High Performance Liquid Chromatography (HPLC) 214

High Performance Liquid Chromatography (HPLC) 214 Introduction High performance liquid chromatography 214 is the most widely used of all of the analytical separation techniques. The reasons for the popularity of the method is its sensitivity, ready adaptability to accurate quantitative determinations, suitability for separating non-volatile species or thermally fragile ones, wide spread applicability to substance that are of prime interest to industry, many fields of science and the public. The applications of chromatography have grown explosively in the last fifty years owing not only to the development of several new types of chromatographic techniques but also to the growing need by scientist for better methods for characterizing complex mixtures. General methodology for the development of new HPLC methods 215-228 HPLC method development follows the series of steps summarized below. Information on sample, objective of separation. Need for special HPLC procedure, sample pretreatment etc. Choice of detector and detector settings. Choosing LC method, preliminary run, estimation of best separation conditions. Optimization of separation conditions. Check for problems or requirement for special procedure. a) Recovery of purified material   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   b) Quantitative calibration  Ã‚  Ã‚  Ã‚  Ã‚   c) Qualitative method Validate method for routine laboratory use. A good method development strategy should require only as many experimental runs as are necessary to achieve the desired final result. Finally, method development should be simple as possible, yet it should allow the use of sophisticated tools such as computer modeling if these are available. Before the beginning of method development, it is necessary to review what is known about the sample in order to define the goals of separation. The kinds of sample related information that can be important are summarized in Table-7.1. Table-8.1 Important information concerning sample composition and properties Number   of compounds present in the sample Chemical structures of components Molecular weights of compounds PKa values of compounds UV spectra of compounds Concentration range of various compounds in samples of interest Sample solubility   Ã‚   The chemical composition of the sample can provide valuable clues for the best choice of initial conditions for an HPLC separation. Objectives of separation The objectives of HPLC separation need to be specified clearly include. The use of HPLC to isolate purified sample components for spectral identification or quantitative analysis. It may be necessary to separate all degradants or impurities from a product for reliable content assay. In quantitative analysis, the required levels of accuracy and precision should be known (a precision of  ± 1 to 2% is usually achievable). Whether a single HPLC procedure is sufficient for raw material or one or more formulations and / or different procedures are desired for the analysis of formulations? When the number of samples for analysis at one time is greater than 10, a run time of less than 20 min. will be oftenly important. Knowledge on the desired HPLC equipment, experience and academic training the operators have. Sample pretreatment and detection Samples for analysis come in various forms such as: Solutions ready for injections. Solutions that require dilution, buffering, addition of an internal standard or other volumetric manipulation. Solids that must first be dissolved or extracted. Samples that require pretreatment to remove interference and/or protect the column or equipment from damage. Most samples for HPLC analysis require weighing and / or volumetric dilution before injection. Best results are often obtained when the composition of the sample solvent is close to that of the mobile phase since this minimizes baseline upset and other problems. Some samples require a partial separation ( pretreatment) prior to HPLC, because of need to remove interference, concentrate sample analytes or eliminate â€Å"column killer†. In many cases the development of an adequate sample pretreatment can be challenging than achieving a good HPLC separation. The detector selected should sense all sample components of interest. Variable-wavelength ultraviolet (UV) detectors normally are the first choice, because of their convenience and applicability for most samples. For this reason information on the UV spectra can be an important aid for method development. When the UV response of the sample is inadequate, other detectors are available (flourescence, electrochemical, PDA etc.) or the sample can be derivatized for enhanced detection. Developing the method for the separation Selecting an HPLC method and initial conditions If HPLC is chosen for the separation, the next step is to classify the sample as regular or special. Regular samples means typical mixtures of small molecules (    Table-8.2 Handling of special sample Sample Requirements Inorganic ions Detection is primary problems; use ion chromatography Isomers Some isomers can be separated by reversed-phase HPLC and are then classified as regular samples; better separations of isomers are obtainable using either (1) normal-phase HPLC or (2) reversed-phase separations with cyclodextrin-silica columns. Enantiomers These compounds require â€Å"chiral† conditions for their separations. Biological Several factors make samples or this kind â€Å"special†; molecular conformation, polar functionality and a wide range of hydrophobicity. Macromolecules â€Å"Big† molecules require column packing with large pores  Ã‚  (>> 10-nm diameters); in addition, biological molecules require special conditions as noted above. Table-8.3 Preferred experimental conditions for the initial HPLC separation Separation variable Preferred initial choice Column Dimensions (length, ID) 15 x 0.46 cm Particle size 5 mma Stationary phase C8 or C18 Mobile phase Solvent A and B Buffer-acetonitrile % B 80-100%b Buffer (compound, pH, concentration) 25mM potassium phosphate 2.0 Additives (e.g., amine modifiers, ion pair reagents) Do not use initially Flow rate 1.5–2.0 ml/min Temperature 35-45 ºC Sample Size Volumed >25 mL Weightd B : Polar solvent  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   a 3.5 mm particles are an alternative using a 7.5 cm column b For an initial isocratic run; an initial gradient run is preferred. c No buffer required for neutral samples; for pH d Smaller values required for smaller-volume columns (e.g., 7.50.46-cm, 3.5-mm column). Table-8.4 Physical properties of silica supports for some C 18 columns Column (mL/mL) Pore diameter (nm) Surface area (m2/g) Percent Porosity Hypersil ODS 12 170 57 LiChrosorb C18 10 355 71 Novapak C18 6 N/Aa N/Aa Nucleosil C18 10 350 69` Symmetry C18 10 335 66 Zorbax ODS 6 300 55 Zorbax Rx, SB, XDB 8 180 50 a N/A : Not available On the basis of the initial exploratory run isocratic or gradient elution can be selected as most suitable. If typical reversed-phase conditions provide insufficient sample retention, suggesting the use of either ion pair on normal phase HPLC. Alternatively, the sample may be strongly retained with 100% acetonitrile as mobile phase, suggesting the use of non-aqueous reversed-phase (NARP) chromatography or normal phase HPLC. Some characteristics of reversed-phase and other HPLC methods are summarized below. Table-8.5 Characteristics of primary HPLC methods Method / description/ columns Preferred method Reversed-phase HPLC Uses water – organic mobile phase Columns: C18 (ODS), C8, phenyl, trimethylsilyl (TMS), Cyano First choice for most samples, especially neutral or non-ionisable compounds that dissolve in water-organic mixtures Ion-pair HPLC Uses water-organic mobile phase a buffer to control pH and an ion pair reagent. Column : C18, C8, cyano. Acceptable choice for ionic or ionizable compounds, especially bases or cations. Normal phase HPLC Uses mixtures of organic solvents as mobile phase Columns: Cyano, diol, amino and silica. Good second choice when reversed-phase or ion-pair HPLC is ineffective, first choice for lipophilic samples that do not dissolve well in water-organic mixtures, first choice for mixtures of isomers and for preparative-scale HPLC (silica best) Getting started on method development One approach is to use an isocratic mobile phase of some average solvent strength (e.g., 50%) organic solvent. A better alternative is to use a very strong mobile phase with (80-100% B), then reduce %B as necessary. The initial separation with 100%B results in rapid elution of the entire sample, but few groups will separate. Decreasing solvent strength shows the rapid separation of all components with a much longer run time, with a broadening of later bands and reduced detection sensitivity. Improving the separation and repeatable separation Generally the chromatographers will consider several aspects of the separation, as summarized in Table-8.6. Table-8.6 Objectives of separation in HPLC method development Objectivesa Comment Resolution Precise and rugged quantitative analysis requires that Rs be greater than 1.5. Separation time Quantitation   Ã‚ £ 2% (1 SD) for assays;  £ 5% for less-demanding analysis;  £15% for trace analysis. Pressure Peak height Narrow peaks are desirable for large signal / noise ratios Solvent consumption   Minimum mobile-phase use per run is desirable. a Roughly in order of decreasing importance but may vary with analysis requirements. Separation or resolution is a primary requirement in quantitative HPLC. The resolution (Rs) value should be maximum (Rs>1.5) favours maximum precision. Resolution usually degrades during the life of the column and can vary from day to day with minor fluctuations in separation conditions. Therefore, values of Rs = 2 or greater should be the goal during method development for simple mixtures. Such resolution will favour both improved assay precision and greater method ruggedness. Some HPLC assays do not require base line separation of the compounds of interest (qualitative analysis). In such cases only enough separation of individual components is required to provide characteristic retention times for peak identification. The time required for a separation (run time = retention time for base band) should be as short as possible and the total time spent on method development is reasonable (runtimes 5 to 10 minutes are desirable). Conditions for the final HPLC method should be selected so that the operating pressure with a new column does not exceed 170 bar (2500 psi) and upper pressure limit below 2000 psi is desirable. There are two reasons for that pressure limit, despite the fact that most HPLC equipment can be operated at much higher pressures. First, during the life of a column, the back pressure may rise by a factor of as much as 2 due to the gradual plugging of the column by particular matter. Second, at lower pressures When dealing with more challenging samples or if the goals of separation are particularly stringent, a large number of method development runs may be required to achieve acceptable separation. Repeatable separation As the experimental runs described above are being carried out, it is important to confirm that each chromatogram can be repeated. When changing conditions (mobile phase, column, and temperature) between method development experiments, enough time must elapse for the column to come into equilibrium with a new mobile phase and temperature. Usually column equilibration is achieved after passage of 10 to 20 column volumes of the new mobile phase through the column. However, this should be confirmed by carrying out a repeat experiment under the same conditions. When constant retention times are observed in two such back-to-back repeat experiments ( ± 0.5% or better), it can be assumed that the column is equilibrated and the experiments are repeatable. Completing the HPLC method development The final procedure should meet all the objectives that were defined at the beginning of method development. The method should also be robust in routine operation and usable by all laboratories and personnel for which it is intended. Quantitation and method validation One of the strengths of HPLC is that is an excellent quantitative analytical technique. HPLC can be used for the quantitation of the primary or major component of a sample (including pure samples) for mixture of many compounds at intermediate concentrations and for the assessment of trace impurity concentrations in matrix. Method validation, according to the United States Pharmacopoeia (USP), is performed to ensure that an analytical methodology is accurate, specific, reproducible and rugged over the specified range that an analyte will be analysed. Method validation provides an assurance of reliability during normal use and is sometimes described as the process of providing documented evidence that the method does what it is intended to do. According to USP, the method validation involves eight steps as given below. Precision Accuracy Limit of detection Limit of quantitation Specificity Linearity and range Ruggedness Robustness Precision and accuracy: Already discussed in chapter-1. Linearity The linearity of the method is a measure of how well a calibration plot of response v/s concentration approximates a straight line, or how well the data fit to the linear equation. Y = aX + b Where ‘Y’ is the response, ‘X’ is the concentration, ‘a’ is the slope and ‘b’ is the intercept of a line fit to the data. Ideally, a linear relationship is preferred (b = 0) because it is more precise, easier for calculations and can be defined with fewer standards. Also, UV detector response for a dilute sample is expected to follow Beer’s law and be linear. Therefore, a linear calibration gives evidence that the system is performing properly throughout the concentration range of interest. Generally in HPLC, if we are using internal standard, then the linearity plot is to be drawn by taking concentration of the analyte on x-axis and the ratio of area under the curve (AUC) of analyte to AUC of internal standard (IS) on y-axis. The resulting plot slope, intercept and correlation coefficient provide the desired information on linearity. A linearity correlation coefficient above 0.999 is acceptable for most methods. Limit of detection (LOD) The limit of detection (LOD) is the smallest concentration that can be detected reliably. The LOD represents the concentration of analyte that would yield a signal-to-noise (S/N) ratio of 3. Limit of quantitation (LOQ) The LOQ is the concentration that can be quantitated reliably with a specified level of accuracy and precision. The LOQ represents the concentration of analyte that would yield a signal-to-noise ratio of 10. LOD and LOQ can be determined by using the following expressions. LOD  Ã‚  Ã‚   =  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   3 X N / B LOQ  Ã‚  Ã‚   =  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   10 X N / B Where N is the noise estimate, is the standard deviation of the peak area ratio of analyte to IS (5 injections) of the drugs. B is the slope of the corresponding calibration curve. The LOD and LOQ values determined during method validation are affected by the separation conditions, columns, reagents and especially instrumentation and data systems. Ruggedness Method ruggedness is defined as the reproducibility of results when the method is performed under actual use conditions. This includes different analysts, laboratories, columns, instruments, sources, chemicals, solvents etc. method ruggedness may not be known when a method is first developed, but insight is obtained during subsequent use of that method. Robustness The concept of robustness of an analytical procedure has been defined by the ICH as â€Å" a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters†. The robustness of a method is the ability to remain unaffected by small changes in parameters such as pH of the mobile phase, temperature, percentage of organic solvent and buffer concentration etc. to determine robustness of the method experimental conditions were purposely altered and chromatographic characteristics were evaluated. To study the pH effect on the retention (K1) of the drug, buffer pH is to be changed by 0.2 units. At certain point, retention will increase at any pH above and below of the pH unit. The effect of temperature on the retention characteristics (K1) of the drug is to be studied by changing the temperature in steps 2 ºC from room temperature to 80 ºC and see the effect of temperature on the resolution and peak shape. Effect of percentage organic strength on retention is to be studied by varying the percentage of organic solvents like acetonitrile, methanol etc. from 0 to 2% while the other mobile phase contents are held constant and observe the K1. At certain point decreases in K1 observed with increase in the level of organic solvent. Effect of buffer concentration should be checked at three concentration levels i.e. 0.025 M, 0.05 M and 0.1 M and observe retention time and resolution. Stability To generate reproducible and reliable results, the samples, standards and reagents used for the HPLC method must be stable for a reasonable time (e.g., One day, one week, one month, depending on the need). For example, the analysis of even a single sample may require 10 or more chromatographic runs to determine system suitability, including standard concentrations to create a working analytical curve and duplicate or triplicate injections of the sample to be assayed. Therefore, a few hours of standard and sample solution stability can be required even for a short (10 min.) separation. When more than one sample is analyzed, automated, over night runs often are performed for better laboratory efficiency. Typically, 24 hours stability is desired for all solutions and reagents that need to be prepared for each analysis. Mobile phases should be chosen to avoid stability problems, especially the use of amine additives or specific solvents. For example, mobile phase containing THF (tetra hydrofuran) are known to be susceptible to oxidation, therefore, the mobile phase should be prepared daily with fresh THF. Some buffered mobile phases cause problems for example, phosphate and acetate provide good media for microbial growth. Sodium oxide (0.1%) is often added to the mobile phase buffer to inhibit such growth, adding more than 5% of organic solvent is also effective. Long term column stability is critical for method ruggedness. Even the best HPLC column will eventually degrade and lose its initial performance, often as a function of the number of samples injected. System suitability System suitability experiments can be defined as tests to ensure that the method can generate results of acceptable accuracy and precision. The requirements for system suitability are usually developed after method development and validation have been completed. The criteria selected will be based on the actual performance of the method as determined during its validation. For example, if sample retention times forms part of the system suitability criteria, their variation (SD) during validation can be determined, system suitability might then require that retention times fall within a  ±3 SD range during routine performance of the method. The USP (2000) defines parameters that can be used to determine system suitability prior to analysis. These parameters include plate number (N), tailing factor, k and / or a, resolution (Rs) and relative standard deviation (RSD) of peak height or peak area for respective injections. The RSD of peak height or area of five injections of standard solution is normally accepted as one of the standard criteria. For an assay method of a major component, the RSD should typically be less than 1% for these five respective injections. The plate number and / or tailing factor are used if the run contains only one peak. For chromatographic separations with more than one peak, such as an internal standard assay or an impurity method, expected to contain many peaks, some measure of separations such as Rs is recommended. Reproducibility of tR or k value for a specific compound also defines system performance. The column performance can be defined in terms of column plate number ‘N’ is defined by N = 5.54 (tR / W ½)2 Where ‘tR’ is the retention time of the peak and ‘W ½Ã¢â‚¬â„¢ is the width of the peak at half peak height. The resolution of two adjacent peaks can be calculated by using the formula Rs = 1.18 (t2-t1) / W0.5.1 +W0.5.2 Where ‘t1’ and ‘t2’ are retention times of the adjacent peaks and W0.5.1 and W0.5.2 are the width of the peaks at half height. Rs = 2.0 or greater is a desirable target for method development. The retention factor k is given by the equation. k = (tR – t0) / t0 where ‘tR’ is the band retention time and t0 is the column dead time. The peak symmetry can be represented in terms of peak asymmetry factor and peak tailing factor, which can be calculated by using the following formula. Peak asymmetry factor = B /A Where ‘B’ is the distance at 50% peak height between leading edge to the perpendicular drawn from the peak maxima and ‘A’ is the width of the peak at half height. According to USP (2000) peak tailing factor can be calculated by using the formula T = W0.05 / 2f Where â€Å"W0.05† is the width of the peak at 5% height and â€Å"f† is the distance from the peak maximum to the leading edge of the peak, the distance being measured at a point 50% of the peak height from the base line. High Performance Liquid Chromatography (HPLC) 214 High Performance Liquid Chromatography (HPLC) 214 Introduction High performance liquid chromatography 214 is the most widely used of all of the analytical separation techniques. The reasons for the popularity of the method is its sensitivity, ready adaptability to accurate quantitative determinations, suitability for separating non-volatile species or thermally fragile ones, wide spread applicability to substance that are of prime interest to industry, many fields of science and the public. The applications of chromatography have grown explosively in the last fifty years owing not only to the development of several new types of chromatographic techniques but also to the growing need by scientist for better methods for characterizing complex mixtures. General methodology for the development of new HPLC methods 215-228 HPLC method development follows the series of steps summarized below. Information on sample, objective of separation. Need for special HPLC procedure, sample pretreatment etc. Choice of detector and detector settings. Choosing LC method, preliminary run, estimation of best separation conditions. Optimization of separation conditions. Check for problems or requirement for special procedure. a) Recovery of purified material   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   b) Quantitative calibration  Ã‚  Ã‚  Ã‚  Ã‚   c) Qualitative method Validate method for routine laboratory use. A good method development strategy should require only as many experimental runs as are necessary to achieve the desired final result. Finally, method development should be simple as possible, yet it should allow the use of sophisticated tools such as computer modeling if these are available. Before the beginning of method development, it is necessary to review what is known about the sample in order to define the goals of separation. The kinds of sample related information that can be important are summarized in Table-7.1. Table-8.1 Important information concerning sample composition and properties Number   of compounds present in the sample Chemical structures of components Molecular weights of compounds PKa values of compounds UV spectra of compounds Concentration range of various compounds in samples of interest Sample solubility   Ã‚   The chemical composition of the sample can provide valuable clues for the best choice of initial conditions for an HPLC separation. Objectives of separation The objectives of HPLC separation need to be specified clearly include. The use of HPLC to isolate purified sample components for spectral identification or quantitative analysis. It may be necessary to separate all degradants or impurities from a product for reliable content assay. In quantitative analysis, the required levels of accuracy and precision should be known (a precision of  ± 1 to 2% is usually achievable). Whether a single HPLC procedure is sufficient for raw material or one or more formulations and / or different procedures are desired for the analysis of formulations? When the number of samples for analysis at one time is greater than 10, a run time of less than 20 min. will be oftenly important. Knowledge on the desired HPLC equipment, experience and academic training the operators have. Sample pretreatment and detection Samples for analysis come in various forms such as: Solutions ready for injections. Solutions that require dilution, buffering, addition of an internal standard or other volumetric manipulation. Solids that must first be dissolved or extracted. Samples that require pretreatment to remove interference and/or protect the column or equipment from damage. Most samples for HPLC analysis require weighing and / or volumetric dilution before injection. Best results are often obtained when the composition of the sample solvent is close to that of the mobile phase since this minimizes baseline upset and other problems. Some samples require a partial separation ( pretreatment) prior to HPLC, because of need to remove interference, concentrate sample analytes or eliminate â€Å"column killer†. In many cases the development of an adequate sample pretreatment can be challenging than achieving a good HPLC separation. The detector selected should sense all sample components of interest. Variable-wavelength ultraviolet (UV) detectors normally are the first choice, because of their convenience and applicability for most samples. For this reason information on the UV spectra can be an important aid for method development. When the UV response of the sample is inadequate, other detectors are available (flourescence, electrochemical, PDA etc.) or the sample can be derivatized for enhanced detection. Developing the method for the separation Selecting an HPLC method and initial conditions If HPLC is chosen for the separation, the next step is to classify the sample as regular or special. Regular samples means typical mixtures of small molecules (    Table-8.2 Handling of special sample Sample Requirements Inorganic ions Detection is primary problems; use ion chromatography Isomers Some isomers can be separated by reversed-phase HPLC and are then classified as regular samples; better separations of isomers are obtainable using either (1) normal-phase HPLC or (2) reversed-phase separations with cyclodextrin-silica columns. Enantiomers These compounds require â€Å"chiral† conditions for their separations. Biological Several factors make samples or this kind â€Å"special†; molecular conformation, polar functionality and a wide range of hydrophobicity. Macromolecules â€Å"Big† molecules require column packing with large pores  Ã‚  (>> 10-nm diameters); in addition, biological molecules require special conditions as noted above. Table-8.3 Preferred experimental conditions for the initial HPLC separation Separation variable Preferred initial choice Column Dimensions (length, ID) 15 x 0.46 cm Particle size 5 mma Stationary phase C8 or C18 Mobile phase Solvent A and B Buffer-acetonitrile % B 80-100%b Buffer (compound, pH, concentration) 25mM potassium phosphate 2.0 Additives (e.g., amine modifiers, ion pair reagents) Do not use initially Flow rate 1.5–2.0 ml/min Temperature 35-45 ºC Sample Size Volumed >25 mL Weightd B : Polar solvent  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   a 3.5 mm particles are an alternative using a 7.5 cm column b For an initial isocratic run; an initial gradient run is preferred. c No buffer required for neutral samples; for pH d Smaller values required for smaller-volume columns (e.g., 7.50.46-cm, 3.5-mm column). Table-8.4 Physical properties of silica supports for some C 18 columns Column (mL/mL) Pore diameter (nm) Surface area (m2/g) Percent Porosity Hypersil ODS 12 170 57 LiChrosorb C18 10 355 71 Novapak C18 6 N/Aa N/Aa Nucleosil C18 10 350 69` Symmetry C18 10 335 66 Zorbax ODS 6 300 55 Zorbax Rx, SB, XDB 8 180 50 a N/A : Not available On the basis of the initial exploratory run isocratic or gradient elution can be selected as most suitable. If typical reversed-phase conditions provide insufficient sample retention, suggesting the use of either ion pair on normal phase HPLC. Alternatively, the sample may be strongly retained with 100% acetonitrile as mobile phase, suggesting the use of non-aqueous reversed-phase (NARP) chromatography or normal phase HPLC. Some characteristics of reversed-phase and other HPLC methods are summarized below. Table-8.5 Characteristics of primary HPLC methods Method / description/ columns Preferred method Reversed-phase HPLC Uses water – organic mobile phase Columns: C18 (ODS), C8, phenyl, trimethylsilyl (TMS), Cyano First choice for most samples, especially neutral or non-ionisable compounds that dissolve in water-organic mixtures Ion-pair HPLC Uses water-organic mobile phase a buffer to control pH and an ion pair reagent. Column : C18, C8, cyano. Acceptable choice for ionic or ionizable compounds, especially bases or cations. Normal phase HPLC Uses mixtures of organic solvents as mobile phase Columns: Cyano, diol, amino and silica. Good second choice when reversed-phase or ion-pair HPLC is ineffective, first choice for lipophilic samples that do not dissolve well in water-organic mixtures, first choice for mixtures of isomers and for preparative-scale HPLC (silica best) Getting started on method development One approach is to use an isocratic mobile phase of some average solvent strength (e.g., 50%) organic solvent. A better alternative is to use a very strong mobile phase with (80-100% B), then reduce %B as necessary. The initial separation with 100%B results in rapid elution of the entire sample, but few groups will separate. Decreasing solvent strength shows the rapid separation of all components with a much longer run time, with a broadening of later bands and reduced detection sensitivity. Improving the separation and repeatable separation Generally the chromatographers will consider several aspects of the separation, as summarized in Table-8.6. Table-8.6 Objectives of separation in HPLC method development Objectivesa Comment Resolution Precise and rugged quantitative analysis requires that Rs be greater than 1.5. Separation time Quantitation   Ã‚ £ 2% (1 SD) for assays;  £ 5% for less-demanding analysis;  £15% for trace analysis. Pressure Peak height Narrow peaks are desirable for large signal / noise ratios Solvent consumption   Minimum mobile-phase use per run is desirable. a Roughly in order of decreasing importance but may vary with analysis requirements. Separation or resolution is a primary requirement in quantitative HPLC. The resolution (Rs) value should be maximum (Rs>1.5) favours maximum precision. Resolution usually degrades during the life of the column and can vary from day to day with minor fluctuations in separation conditions. Therefore, values of Rs = 2 or greater should be the goal during method development for simple mixtures. Such resolution will favour both improved assay precision and greater method ruggedness. Some HPLC assays do not require base line separation of the compounds of interest (qualitative analysis). In such cases only enough separation of individual components is required to provide characteristic retention times for peak identification. The time required for a separation (run time = retention time for base band) should be as short as possible and the total time spent on method development is reasonable (runtimes 5 to 10 minutes are desirable). Conditions for the final HPLC method should be selected so that the operating pressure with a new column does not exceed 170 bar (2500 psi) and upper pressure limit below 2000 psi is desirable. There are two reasons for that pressure limit, despite the fact that most HPLC equipment can be operated at much higher pressures. First, during the life of a column, the back pressure may rise by a factor of as much as 2 due to the gradual plugging of the column by particular matter. Second, at lower pressures When dealing with more challenging samples or if the goals of separation are particularly stringent, a large number of method development runs may be required to achieve acceptable separation. Repeatable separation As the experimental runs described above are being carried out, it is important to confirm that each chromatogram can be repeated. When changing conditions (mobile phase, column, and temperature) between method development experiments, enough time must elapse for the column to come into equilibrium with a new mobile phase and temperature. Usually column equilibration is achieved after passage of 10 to 20 column volumes of the new mobile phase through the column. However, this should be confirmed by carrying out a repeat experiment under the same conditions. When constant retention times are observed in two such back-to-back repeat experiments ( ± 0.5% or better), it can be assumed that the column is equilibrated and the experiments are repeatable. Completing the HPLC method development The final procedure should meet all the objectives that were defined at the beginning of method development. The method should also be robust in routine operation and usable by all laboratories and personnel for which it is intended. Quantitation and method validation One of the strengths of HPLC is that is an excellent quantitative analytical technique. HPLC can be used for the quantitation of the primary or major component of a sample (including pure samples) for mixture of many compounds at intermediate concentrations and for the assessment of trace impurity concentrations in matrix. Method validation, according to the United States Pharmacopoeia (USP), is performed to ensure that an analytical methodology is accurate, specific, reproducible and rugged over the specified range that an analyte will be analysed. Method validation provides an assurance of reliability during normal use and is sometimes described as the process of providing documented evidence that the method does what it is intended to do. According to USP, the method validation involves eight steps as given below. Precision Accuracy Limit of detection Limit of quantitation Specificity Linearity and range Ruggedness Robustness Precision and accuracy: Already discussed in chapter-1. Linearity The linearity of the method is a measure of how well a calibration plot of response v/s concentration approximates a straight line, or how well the data fit to the linear equation. Y = aX + b Where ‘Y’ is the response, ‘X’ is the concentration, ‘a’ is the slope and ‘b’ is the intercept of a line fit to the data. Ideally, a linear relationship is preferred (b = 0) because it is more precise, easier for calculations and can be defined with fewer standards. Also, UV detector response for a dilute sample is expected to follow Beer’s law and be linear. Therefore, a linear calibration gives evidence that the system is performing properly throughout the concentration range of interest. Generally in HPLC, if we are using internal standard, then the linearity plot is to be drawn by taking concentration of the analyte on x-axis and the ratio of area under the curve (AUC) of analyte to AUC of internal standard (IS) on y-axis. The resulting plot slope, intercept and correlation coefficient provide the desired information on linearity. A linearity correlation coefficient above 0.999 is acceptable for most methods. Limit of detection (LOD) The limit of detection (LOD) is the smallest concentration that can be detected reliably. The LOD represents the concentration of analyte that would yield a signal-to-noise (S/N) ratio of 3. Limit of quantitation (LOQ) The LOQ is the concentration that can be quantitated reliably with a specified level of accuracy and precision. The LOQ represents the concentration of analyte that would yield a signal-to-noise ratio of 10. LOD and LOQ can be determined by using the following expressions. LOD  Ã‚  Ã‚   =  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   3 X N / B LOQ  Ã‚  Ã‚   =  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   10 X N / B Where N is the noise estimate, is the standard deviation of the peak area ratio of analyte to IS (5 injections) of the drugs. B is the slope of the corresponding calibration curve. The LOD and LOQ values determined during method validation are affected by the separation conditions, columns, reagents and especially instrumentation and data systems. Ruggedness Method ruggedness is defined as the reproducibility of results when the method is performed under actual use conditions. This includes different analysts, laboratories, columns, instruments, sources, chemicals, solvents etc. method ruggedness may not be known when a method is first developed, but insight is obtained during subsequent use of that method. Robustness The concept of robustness of an analytical procedure has been defined by the ICH as â€Å" a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters†. The robustness of a method is the ability to remain unaffected by small changes in parameters such as pH of the mobile phase, temperature, percentage of organic solvent and buffer concentration etc. to determine robustness of the method experimental conditions were purposely altered and chromatographic characteristics were evaluated. To study the pH effect on the retention (K1) of the drug, buffer pH is to be changed by 0.2 units. At certain point, retention will increase at any pH above and below of the pH unit. The effect of temperature on the retention characteristics (K1) of the drug is to be studied by changing the temperature in steps 2 ºC from room temperature to 80 ºC and see the effect of temperature on the resolution and peak shape. Effect of percentage organic strength on retention is to be studied by varying the percentage of organic solvents like acetonitrile, methanol etc. from 0 to 2% while the other mobile phase contents are held constant and observe the K1. At certain point decreases in K1 observed with increase in the level of organic solvent. Effect of buffer concentration should be checked at three concentration levels i.e. 0.025 M, 0.05 M and 0.1 M and observe retention time and resolution. Stability To generate reproducible and reliable results, the samples, standards and reagents used for the HPLC method must be stable for a reasonable time (e.g., One day, one week, one month, depending on the need). For example, the analysis of even a single sample may require 10 or more chromatographic runs to determine system suitability, including standard concentrations to create a working analytical curve and duplicate or triplicate injections of the sample to be assayed. Therefore, a few hours of standard and sample solution stability can be required even for a short (10 min.) separation. When more than one sample is analyzed, automated, over night runs often are performed for better laboratory efficiency. Typically, 24 hours stability is desired for all solutions and reagents that need to be prepared for each analysis. Mobile phases should be chosen to avoid stability problems, especially the use of amine additives or specific solvents. For example, mobile phase containing THF (tetra hydrofuran) are known to be susceptible to oxidation, therefore, the mobile phase should be prepared daily with fresh THF. Some buffered mobile phases cause problems for example, phosphate and acetate provide good media for microbial growth. Sodium oxide (0.1%) is often added to the mobile phase buffer to inhibit such growth, adding more than 5% of organic solvent is also effective. Long term column stability is critical for method ruggedness. Even the best HPLC column will eventually degrade and lose its initial performance, often as a function of the number of samples injected. System suitability System suitability experiments can be defined as tests to ensure that the method can generate results of acceptable accuracy and precision. The requirements for system suitability are usually developed after method development and validation have been completed. The criteria selected will be based on the actual performance of the method as determined during its validation. For example, if sample retention times forms part of the system suitability criteria, their variation (SD) during validation can be determined, system suitability might then require that retention times fall within a  ±3 SD range during routine performance of the method. The USP (2000) defines parameters that can be used to determine system suitability prior to analysis. These parameters include plate number (N), tailing factor, k and / or a, resolution (Rs) and relative standard deviation (RSD) of peak height or peak area for respective injections. The RSD of peak height or area of five injections of standard solution is normally accepted as one of the standard criteria. For an assay method of a major component, the RSD should typically be less than 1% for these five respective injections. The plate number and / or tailing factor are used if the run contains only one peak. For chromatographic separations with more than one peak, such as an internal standard assay or an impurity method, expected to contain many peaks, some measure of separations such as Rs is recommended. Reproducibility of tR or k value for a specific compound also defines system performance. The column performance can be defined in terms of column plate number ‘N’ is defined by N = 5.54 (tR / W ½)2 Where ‘tR’ is the retention time of the peak and ‘W ½Ã¢â‚¬â„¢ is the width of the peak at half peak height. The resolution of two adjacent peaks can be calculated by using the formula Rs = 1.18 (t2-t1) / W0.5.1 +W0.5.2 Where ‘t1’ and ‘t2’ are retention times of the adjacent peaks and W0.5.1 and W0.5.2 are the width of the peaks at half height. Rs = 2.0 or greater is a desirable target for method development. The retention factor k is given by the equation. k = (tR – t0) / t0 where ‘tR’ is the band retention time and t0 is the column dead time. The peak symmetry can be represented in terms of peak asymmetry factor and peak tailing factor, which can be calculated by using the following formula. Peak asymmetry factor = B /A Where ‘B’ is the distance at 50% peak height between leading edge to the perpendicular drawn from the peak maxima and ‘A’ is the width of the peak at half height. According to USP (2000) peak tailing factor can be calculated by using the formula T = W0.05 / 2f Where â€Å"W0.05† is the width of the peak at 5% height and â€Å"f† is the distance from the peak maximum to the leading edge of the peak, the distance being measured at a point 50% of the peak height from the base line.

Nation of Islam in the Light of Elijah Muhammad Essay -- James Baldwin

Nation of Islam in the Light of Elijah Muhammad In 1961 James Baldwin met Elijah Muhammad, the leader of the Nation of Islam movement at the time. Baldwin’s experience within the Christian Church prior to his meeting with Elijah helped him analyze the Nation of Islam. This also allowed him to draw parallels between the Nation of Islam movement and the Christian Church. How James Baldwin understood the way the Christian Church worked, and a close look at the Nation of Islam, brings to light the credibility of organized religions. In 1930 Wallace D. Fard gave birth to the Nation of Islam movement. He began in Detroit going door to door preaching to black families about his remedy for their problems. He tried replacing their beliefs with his own, for solving their problems. Fard had three main ideas that laid the foundation for his â€Å"remedy†. He wanted black separatism, everyone to know that white men are evil (which was not hard for African Americans to believe since the idea already lived within their minds), and to show the inadequacy of Christianity to African Americans. During this period Fard recruited Elijah Poole, changed Elijah’s name to Elijah Muhammad and developed him into his Chief Minister. With the mysterious disappearance of Fard in 1934, Elijah took over the movement. Elijah was born in Sandersville, Georgia in 1897 as the seventh of twelve children. He barely finished the third grade before dropping out to work in the fields to help support his family (Muh ammad 1+). During his childhood Elijah witnessed a lynching right before his eyes; different accounts vary on whom he actually saw lynched. In Baldwin’s account in â€Å"Down at the Cross,† he says he saw his father lynched befo... ...1961 . Kihss, Peter. â€Å"Negro Extremist Groups Step Up Nationalist Drive.† New York Times. 2. ProQuest. New York Times (1857-Current file). New York, NY. 1 Mar. 1961 . Muhammad, Mother Tynetta. A Historical Look at the Honorable Elijah Muhammad. 1+. 28 March 1996. Nation of Islam. 10 March 2004. . Pement, Eric. â€Å"Louis Farrakhan and the Nation of Islam: Part One.† Cornerstone. 1997, vol. 26, issue 111, p. 10-16, 20. . Pement, Eric. â€Å"Louis Farrakhan and the Nation of Islam: Part Two.† Cornerstone. 1997, vol. 26, issue 112, p. 32-36, 38. . Pipes, Daniel. â€Å"How Elijah Muhammad Won.† Commentary. Jun. 2000, vol. 109 issue 6, p31, 6p. Academic Search Elite. EBSCOhost. .

Delaware :: essays research papers

Delaware Delaware is a really cool state. I say that because there is not a whole-lot of crime there and for country folks it’s great because there is a lot of cows and pigs, but there are also a lot of cars there too. It was some rivers and creeks land definition and tons of history, but there isn’t very many people there compared to California. Delaware has gained 2 nicknames over the years, The First State and The Diamond State. It got the nickname The First State because it was the first state to ratify the constitution. It got the nickname the Diamond State because they are the world leaders in diamond mining. Delaware was some really neat geography because they have swamps, rivers, lakes, but they really don’t really have a lot mountains. They have the biggest natural cypress swamp in the world and Pocomoke Swamp the northern most swamp in the United States. They have a couple rivers the Christina and Brandywine Creek. As for lakes the have Chesapeake Bay and Delaware Bay. Delaware has a lot of economic activity. More than 80% of Delaware’s farm income is from the production of broiler chickens and a variety of other things including soybeans, greenhouse products and corn. Milk is also produced considering that Delaware was more cows than they know what to do with. Fishing is declining but crabs, shad, cod, oysters and clams are caught. Delaware has many useful industries. Delaware industries major in food processing, primary metals, machinery, leather goods, fabricated metals, printing and publishing. They also make a whole- lot of textiles like linoleum. They also make a lot of chemicals and cars. They are one of the most popular car states in the United States. Delaware’s climate is on the cold side with the average temperature in January is 32 and 72 in July. Delaware is also on the storm track of the Gulf of Mexico. Delaware’s average rainfall is about 44 inches. Delaware has common natural resources. Kaolin is the most significant natural resource followed by granite, gravel, and clay (used to make brick and tiles). Hydroelectric power hasn’t been developed yet. The Coastal Zone act was passed in 1971. Communications in Delaware are simple. Delaware has 2 daily newspaper and several weeklies. Public Television is very popular in Delaware. Of course they also have phones and faxes and stuff like that.

A Biographical Analysis of The Rime of the Ancient Mariner Essays

A Biographical Analysis of The Rime of the Ancient Mariner â€Å"The Rime of the Ancient Mariner,† by Samuel Taylor Coleridge, is a somewhat lengthy poem concerning the paranormal activities of a sea mariner and his crew. The work was constructed to be the beginning piece in Lyrical Ballads, a two-volume set written by William Wordsworth and Coleridge. Wordsworth intended to, in his volume, make the ordinary seem extraordinary, while Coleridge aimed to make the extraordinary ordinary. â€Å"The Rime† was first published in 1798. Despite the current popularity of the piece, it was harshly criticized upon being first published. One of â€Å"The Rime’s† toughest opponents was Wordsworth himself, who claimed that the poem had â€Å"neither characterization nor proper agency nor skill in the handling of imagery† (Fry, 12). Wordsworth even bluntly described the piece as being in the wrong overall meter (Fry, 12). Because of these presumed flaws, â€Å"The Rime† was edited into several subsequent editions, being released in 1800, 1802, 1805, 1817, and 1834. When a reader examines â€Å"the Rime,† the piece first appears to be merely that of an archaic ghost story. Throughout the years though, many have analyzed the poem from various angles of interpretation. Some of the methods used to decipher â€Å"The Rime† have included reader-response, Marxist, new historicism, psychoanalytic, and even deconstruction analysis. While each of these alternatives provides an individualistic prospective on the poem, they are all somewhat different, and can even be objective at times depending on the reader in question. While â€Å"The Rime† may have been constructed to address slavery, the economy, or even morality, it can also be greatly appreciated when looke... ...ations of his work (Fry, 8). A short time later, Coleridge died, but only after some of the most peaceful years of his life. â€Å"The Rime† is a supernaturally based poem, which is full of imaginative symbolism and imagery. Despite its numerous revisions, it is still a defining piece of literature from the Romantic period. While several approaches can be taken to investigate the poem, a biographical analysis provides an insightful look into the life of the author that created the work. In â€Å"The Rime,† Coleridge has the Mariner facing many of the same obstacles that he faced throughout his life, including death, isolation, constant wandering, and a final search for salvation. Works Cited Coleridge, Samuel. â€Å"The Rime of the Ancient Mariner.† Fry 26-75. Fry, Paul, ed. The Rime of the Ancient Mariner. Boston and New York: Bedford / St. Martin’s, 1999.

Personal Protective Equipment and Good Personal Hygiene

Unit ICO1 The principles of infection prevention and control Outcome 1 Understand roles and responsibilities in the prevention and control of infections The learner can: 1. explain employees’ roles and responsibilities in relation to the prevention and control of infection 2. explain employers’ responsibilities in relation to the prevention and control infection. Outcome 2 Understand legislation and policies relating to prevention and control of infections The learner can: 1. utline current legislation and regulatory body standards which are relevant to the prevention and control of infection 2. describe local and organisational policies relevant to the prevention and control of infection. Outcome 3 Understand systems and procedures relating to the prevention and control of infections The learner can: 1. describe procedures and systems relevant to the prevention and control of infection 2. explain the potential impact of an outbreak of infection on the individual and th e organisation.Outcome 4 Understand the importance of risk assessment in relation to the prevention and control of infections The learner can: 1. define the term risk 2. outline potential risks of infection within the workplace 3. describe the process of carrying out a risk assessment 4. explain the importance of carrying out a risk assessment. Outcome 5 Understand the importance of using Personal Protective Equipment (PPE) in the prevention and control of infections The learner can: 4. tate current relevant regulations and legislation relating to PPE 5. describe employees’ responsibilities regarding the use of PPE 6. describe employers’ responsibilities regarding the use of PPE 7. describe the correct practice in the application and removal of PPE 8. describe the correct procedure for disposal of used PPE. Outcome 6 Understand the importance of good personal hygiene in the prevention and control of infections The learner can: 1. describe the key principles of good per sonal hygiene

Aging Aircraft and Structural Failures

Aloha Airlines Flight 243: Structural Failure of an Aging Aircraft Safety 335 aloha Airlines Flight 243: Structural Failure of an Aging Aircraft The age of the United States' commercial aircraft fleet is a serious problem. The average age of commercial airline fleets is continuing to increase. As of year 2000, more than 2,500 commercial aircraft in the United States were flying beyond their original design lives. In 1988, a major incident in which the top peeled off an Aloha Airlines Boeing 737 in flight, sweeping a flight attendant to her death, was blamed on weak maintenance of the old aircraft's structure.The flight attendant was swept overboard at 24,000 feet after a spontaneous failure of one of the aircraft's longitudinal joints. The aircraft involved, a Boeing 737, had been subjected to the severe operating environment particular to inter-island service during its 19-year lifespan. The Aloha Airlines 737 was the second oldest aircraft still in service. The aircraft, which had been designed for 75,000 flight cycles, had actually accumulated 89,680 cycles with stage lengths of 20 to 40 minutes. This intensive use also inflicts the loads associated with repeated pressurization and de-pressurization of the aircraft's cabin.Fuselage fatigue damage is primarily caused by the application of the pressurization cycle that occurs on each flight. Typically, the inter-island carriers fly at 23,000 ft while the cabin is pressurized to 8,000 creating a 5 psi differential. The fuselage of this aircraft suffered from extensive Multiple Site Damage (MSD). MSD occurs when stress factors are fairly uniform, so that small cracks appear and grow at roughly the same rate. Each individual crack is difficult to see and by itself poses little problem; however, the small cracks can join together to form a large crack (Oster, Clinton, Strong, Zorn, 1992).The Aloha 737's MSD's were cracks extending on both sides of rivet holes along the upper row of the lap joints along the fuselag e. Two other major fuselage failures existed on the upper row of rivets on the S10L lap joint. Near the forward entry door, the MSD cracks had joined to form a single crack about 6-8 inches long. Two passengers noticed this crack as they boarded the aircraft in Hilo, HI. The crack was long enough and wide enough that the internal fiberglass insulation was being extruded from it. The passengers did not report the crack, feeling that if the aircraft was not safe, the airline would obviously not fly it (NTSB, 1988).The focus of the National Transportation Safety Board's (NTSB) hearings were the failure of the Boeing 737's design to Safely Decompress. Contrary to the NTSB findings, the fuselage did tear open a Safe Decompression Flap as designed. If the Flight Attendant had not been standing directly underneath the Flap when it occurred, the plane would probably not have suffered an explosive decompression (Hinder, 2000). The forces exerted on the fuselage by leveling of the aircraft wa s the final blow that caused a link up of MSD cracks at BS500 (Approximately Row 5) which were arrested by the Safe Decompression design causing the Flap to open.At the instant in time represented by Figure 1, the aircraft is in the process of rotating from climb to level flight, there is a tear in the S10L lap joint at approximately in front of row 1 and a Safe Decompression Flap at approximately Row 5. [pic] Figure 1 The cabin was pressurized. With the approximately 10†³ x10†³ opening, the internal cabin air began to escape at over 700 mph. The Flight Attendant who was reaching to pick up a cup from Passenger 5B was immediately sucked into but not through the Safe Decompression Flap. Only the Flight Attendant's right arm and head were forced through the opening.This effectively slammed the door shut on a 700 mph jet stream. The resultant reaction to corking a high velocity fluid flow is called a Fluid Hammer. The attempt to stop the high velocity airflow causes a pressur e spike of high value (hundreds of pounds per square inch) and short duration (only tens of thousandths of a second). The fuselage integrity was severely degraded due to the MSD and its 0. 036†³ (36 thousandths of an inch) pressure boundary wall thickness is only designed for about 8. 5 psi normal operating pressure differential. The fuselage could barely contain the normal operating pressure.The Fluid Hammer caused the fuselage skin to crack (Hinder, 2000). Fluid flow always follows the path of least resistance. With the Flap at row 5 plugged and the fuselage skin between in front of row 1 and row 5 completely severed, the internal cabin pressure begins to push outward on the fuselage skin, sensing the weakest point as halfway between in front of row 1 and row 5. This is the location identified by the NTSB as the probable location of the initial failure. For the next 0. 6 seconds (6 tenths of a second) the aircraft is propelled nose down and to the right by the internal air es caping from the disintegrating fuselage.The Flight Attendant begins to slide toward the rear of the aircraft as the lap joint separates. See Figure 2. [pic] Figure 2 For the next 1. 2 seconds the aircraft the moves up and to the left as sections of the fuselage continue to peel away. The section between row 1 and row 5 blows out and downward. The roof section blows up, tearing from the row 1 seam. At row 5, the roof crack angles diagonally back toward the top centerline of the aircraft. Aft of row 5, along the lap joint, above the joint, a diagonal piece folds back over on itself.Below the joint, the window belt section tears in a backward direction. The Flight Attendant continues to slide rearward. See Figure 3. [pic] Figure 3 The window belt section aft of row 5 and below the lap-joint folds back over rearward. This pops out the window just forward of the row 6 seam and tears the fuselage from the window to the lap joint. This allows the Flight Attendant's head and body to drop ap proximately 1 foot just as the section slams against the exterior fuselage. See Figure 4. [pic] Figure 4 The pilots told of a sudden whooshing sound at 24,000 ft. flying debris in the cockpit and a bouncing 25-mile descent with one engine out. The flight was diverted to Maui and a successful landing was accomplished with a significant portion of the fuselage missing. Sixty-nine of the 95 passengers sustained injuries from flailing wires, metal strips and wind burn (Hinder, 2000). According to the NTSB's report on the investigation, contributing factors were improper inspection by company maintenance personnel, inadequate supervision of maintenance personnel, inadequate supervision by the FAA and inadequate aircraft equipment from the manufacturer.Numerous other structural failure incidents of note in the same time period also brought to light significant problems to be addressed. In October 1988, a foot long crack was noted in a B-737 while stripping paint. In December 1988, a B-727 was noted with a 14†³ crack in the fuselage. In February 1989, a B-747 cargo door failed, the fuselage was torn off and nine passengers were sucked to their deaths. In July 1989, a pre-flight inspection revealed a 20†³ long fatigue crack in the wing of a B-727 (Oster, et al, 1992).Though durability and damage tolerance were issues prior to this, the Aloha incident is generally considered to be the start of the Federal Aviation Authorities (FAA) Focused Aging Aircraft Program. The first response to the accident was an industry-wide review of the adequacy of aircraft design and efficacy of maintenance programs. In general, the aviation community found that with proper maintenance and structural modifications and with attention to service related damage such as fatigue and corrosion, the service lives of airplanes could be safely extended (Seher, Smith, 2001).To identify and rectify issues related to operation of aircraft beyond their designed service objectives, the Air Wor thiness Assurance Working Group (AAWG), the National Aging Aircraft Program, and the National Aging Aircraft Research Programs were established. The National Aeronautical and Space Administration (NASA) and the United States Air Force joined in and concentrated on research in fatigue and fracture issues associated with crack initiation, crack growth and residual strength of multi-site damaged fuselage skins (Seher, Smith, 2001).Though progress has been made in the area of aging aircraft, the continued desire to maintain aircraft in revenue service beyond their design service objectives and the poor financial performance of carriers, there will almost certainly be new structural integrity problems. It is the mission of the FAA's Aging Aircraft and Continued Airworthiness Programs to ensure that age-related problems are predicted and eliminated or mitigated prior to their having a major impact on safety. References Hinder, Prof. , (2000, January 17).Flight 243 Separation Sequence, Pos ted to Disaster city, archived at www. disastercity. com. National Transportation Safety Board Report Identification: DCA88MA054-AAR-89/03. Air Carrier Aloha Airlines Inc. , April 28, 1988, Maui, HI. Oster, C. , Strong, J. , Zorn, K. , (1992), Why Airplanes Crash, Aviation Safety in a Changing World, Oxford University Press, Oxford. Seher, C. , Smith, C. , (2001), Managing the Aging Aircraft Problem, Symposium on Aging Mechanisms and Control, Manchester, England.

Qa 380 Quiz 1

* T * PERFORMANCE measures that are established for a process are known as metrics. T * Once a process is identified, defined, evaluated, and redesigned, the benefits of the process analysis cycle are realized. F * A service blueprint is a flowchart of a service process that shows which of its steps has high customer contact. T * The general principle that 80% of a company’s revenue is generated by 20% of its customers is known as the pareto concept. * A fishbone diagram identifies which category is most frequently observed out of all the categories for which you have data. F . a voluntary system by which employees submit their ideas on process improvements is used in the: opportunity identification phase of process analysis 2. the step in process analysis that immediately follows the process documentation phase is the : evaluate performance phase 3. the resources that management assigns to improving or reengineering the process should: match the process’s scope 4. proc ess analysis focuses on: how work is actually done 5. an effective tool for showing steps of a service process with a high level of customer contact is: service blueprint 6. hich one of the following statements concerning flowcharts is NOT true. The dotted line of visibility separates activities subcontracted form those done in house 7. all of the following are steps in setting a time standard using the time study method EXCEPT: Consulting cost accounting data 8. the manager of a supermarket would like to know which of several quality problems to address first. A tool that would be most helpful would be a: perato chart 9. a restaurant manager tracks complaints from the diner satisfaction cards that are turned in at each table.The data collected from the past week’s diners appear 10. the first step of the systematic approach to process analysis is (opportunity) 11. process (scope) is the boundary of the process to be analyzed. 12. A voluntary system by which employee submit th eir ideas on process improvements is called a (suggestion system) 13. (Metrics) are performance measures that are established for a process and he steps within it. 14. A group of people, who are knowledgeable about the process, meets to propose ideas for change in a rapid-fire manner. Such a session is called (brainstorming)