Performance Characteristics of Methods of Analysis Used for Regulatory Purposes. I. Drug Dosage Forms. C. Automated Methods

1985 ◽  
Vol 68 (1) ◽  
pp. 112-121
Author(s):  
William Horwitz ◽  
Richard Albert
Keyword(s):  
Computer Program ◽  
Drug Dosage ◽  
Dosage Forms ◽  
Performance Characteristics ◽  
Methods Of Analysis ◽  
Collaborative Studies ◽  
Relative Standard ◽  
Standard Deviations ◽  
Best Fit ◽  
Automated Methods

Abstract For analysis of drug dosage forms, precision measures of AOAC approved automated methods, usually containing a spectrophotometric or fluorometric measurement step, were recalculated on a consistent statistical basis, using a computer program "FDACHEMIST." Ten collaborative studies of 14 compounds in 38 materials, consisting of various dosage forms, usually in 10 replications by an average of 7 laboratories, with a total of 2461 determinations, were reviewed. The average relative standard deviations within-laboratory (RSD0) and among-laboratories (RSDX) were 1.1 and 1.9%, respectively, and the ratio of RSD„/RSDX was 0.57, with an average outlier rate of 0.57% of the reported values. The line of best fit for RSDX plotted against — log concentration increases slightly with decreasing concentration, extending from an RSDX of about 1.6% at 100% concentration to an RSDX of 2.2% at 0.1% concentration, a change in RSDX of about 0.2% for a 10-fold decrease in concentration, independent of analyte and matrix.

Performance Characteristics of Methods of Analysis Used for Regulatory Purposes. I. Drug Dosage Forms. F. Gravimetric and Titrimetric Methods

1988 ◽  
Vol 71 (3) ◽  
pp. 619-635 ◽  
Author(s):  
Michel Margosis ◽  
William Horwitz ◽  
Richard Albert
Keyword(s):  
Pharmaceutical Preparations ◽  
Drug Dosage ◽  
Drug Analysis ◽  
Dosage Forms ◽  
Fractional Concentration ◽  
Collaborative Studies ◽  
Relative Standard ◽  
The Difference ◽  
Instrumental Methods ◽  
Best Fit

Abstract The original gravimetric and titrimetric methods approved by AOAC for the analysis of pharmaceutical preparations, particularly during the period 1915-1950, show precision, recovery, and outlier parameters approximately the same as those exhibited by the previously reviewed instrumental methods that are currently used. Fifty-nine published collaborative studies utilized gravimetric methods and 85 used titrimetric. The studies of the gravimetric methods encompassed 47 analytes, 95 dosage forms, and 136 assays; the corresponding figures for the titrimetric studies are 72, 112, and 152. An average of approximately 7 laboratories participated per study. The line of best fit of the relative standard deviation between-laboratories (RSDR) plotted against the negative logarithm of the fractional concentration, C, extends from 1.2 and 1.0% for the gravimetric and titrimetric methods, respectively, at 100% concentration to 2.2 and 2.8% at 1.0% concentration. Below this concentration the precision of the titrimetric methods degenerates faster than that of the gravimetric methods. Above about 0.1% concentration the gravimetric and titrimetric methods are somewhat more precise than the instrumental methods in current use for drug analysis. The difference, however, is not statistically significant and the general equation, RSDR = 2 exp(l - 0.5 log C), is also applicable to gravimetric and titrimetric methods above a concentration level of about C = 0.001 (0.1%)

Performance Characteristics of Methods of Analysis Used for Regulatory Purposes. I. Drug Dosage Forms. E. Miscellaneous Methods

1985 ◽  
Vol 68 (5) ◽  
pp. 830-838
Author(s):  
William Horwitz ◽  
Richard Albert
Keyword(s):  
Standard Deviation ◽  
Relative Standard Deviation ◽  
General Relation ◽  
Drug Dosage ◽  
Dosage Forms ◽  
Allergenic Protein ◽  
Collaborative Studies ◽  
Relative Standard ◽  
Instrumental Methods ◽  
Best Fit

Abstract Precision parameters of miscellaneous methods for the analysis of drug dosage forms approved by AOAC since 1972, and not previously reviewed in this series, were recalculated on a consistent statistical basis by using the computer program FDACHEMIST. Seventeen published collaborative studies were reviewed; the studies encompassed 19 analytes in 80 different materials (dosage forms), 102 collaborative assays, approximately 10 laboratories per study, and principally direct spectrophotometric, polarographic, and spectroscopic methods, for a total of 1451 determinations. The average repeatability relative standard deviation (within-laboratories, RSD„) for the instrumental methods was 1.5%; the reproducibility relative standard deviation (among-laboratories, including within-, RSDX) was 2.6%; the ratio RSD„/RSDX of the averages was 0.57, with an average outlier rate of 2.7% of the reported determinations. The line of best fit of RSDX for the instrumental methods plotted against the negative logarithm of the concentration increases slightly with decreasing concentration, extending from an RSDX of approximately 2.0% at 100% concentration to an RSDX of 3.4% at 0.001% (10 ppm) concentration; this represents an RSDX change of approximately 0.3% (absolute) for each 10-fold decrease in concentration, independent of analyte, matrix, and method. A method for determining precipitated allergenic protein by the micro-Kjeldahl technique appeared to be outside this general relation, showing an RSDX of about 13% at a concentration of 0.015% (150 ppm) nitrogen.

Performance Characteristics of Methods of Analysis Used for Regulatory Purposes. I. Drug Dosage Forms. B. Gas Chromatographic Methods

1984 ◽  
Vol 67 (3) ◽  
pp. 648-652
Author(s):  
William Horwitz ◽  
Richard Albert
Keyword(s):  
Coefficient Of Variation ◽  
Internal Standard ◽  
Drug Dosage ◽  
Dosage Forms ◽  
Chromatographic Methods ◽  
Collaborative Studies ◽  
Simple Extraction ◽  
Standard Solution ◽  
Best Fit

Abstract Gas chromatographic methods for the analysis of drug dosage forms consist of a simple extraction, dilution with an internal standard solution, and injection, or, even simpler, dilution with the internal standard solution and injection. These methods were used in 7 collaborative studies of the determination of 12 pharmaceuticals, published in the Journal of the AOAC during 1973–1983. A total of 43 individual materials consisting of various dosage forms were each analyzed, usually in duplicate, by an average of 8 laboratories, with a total of 582 reported determinations. The average within-laboratory coefficient of variation (CVo) was 1.25% and the average among-laboratories coefficient of variation (CVx) was 2.41%, for a CVo/CVx ratio of 0.52, at an average outlier rate of 1.4% of the reported values. The line of best fit for CVx plotted against concentration increases with decreasing concentration, extending from a CVx of approximately 1.8% at 100% concentration to a CVx of approximately 3.2% at 1% concentration. The change in CVx for a 10-fold decrease in concentration is approximately 0.7% CVx, independent of analyte and matrix.

Performance Characteristics of Methods of Analysis Used for Regulatory Purposes.I. Drug Dosage Forms. D. High Pressure Liquid Chromatographic Methods

1985 ◽  
Vol 68 (2) ◽  
pp. 191-198 ◽  
Author(s):  
William Horwitz ◽  
Richard H Albert
Keyword(s):  
High Pressure ◽  
Standard Deviation ◽  
Relative Standard Deviation ◽  
Drug Dosage ◽  
Dosage Forms ◽  
High Pressure Liquid Chromatographic ◽  
Chromatographic Methods ◽  
Collaborative Studies ◽  
Relative Standard ◽  
Liquid Chromatographic

Abstract Precision parameters of high pressure liquid chromatographic methods approved by AOAC for the analysis of drug dosage forms were recalculated on a consistent statistical basis, using the computer program "FDACHEMIST." Eleven collaborative studies of 12 compounds in 66 dosage forms analyzed by an average of 9 laboratories per study, with a total of 1150 determinations, were reviewed. For the approved methods and methods awaiting approval (9 studies, 11 compounds, 54 dosage forms, and 959 determinations), the average repeatability relative standard deviation (within-laboratory; RSDo) was 1.0%; reproducibility relative standard deviation (among-laboratories, including within-; RSDX) was 2.5%; the ratio RSD„/RSDX was an unusually low 0.40, with an average outlier rate of 0.6% of the reported values. The line of best fit for RSDX plotted against — log concentration increases with decreasing concentration, extending approximately from RSDX =2% at 100% concentration to RSDX = 3.6% at 0.01% concentration,a change in RSDX of about 0.4% for each 10-fold decrease in concentration,independent of analyte and matrix.

scholarly journals Development and Validation of Spectrophotometric Methods for Determination of Fluoxetine, Sertraline, and Paroxetine in Pharmaceutical Dosage Forms

2005 ◽  
Vol 88 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Ibrahim A Darwish
Keyword(s):  
Correlation Coefficients ◽  
Dosage Forms ◽  
Pharmaceutical Dosage Forms ◽  
Factors Affecting ◽  
Spectrophotometric Methods ◽  
Linear Relationships ◽  
Relative Standard ◽  
Optimum Reaction ◽  
Standard Deviations

Abstract Three simple and sensitive spectrophotometric methods were developed and validated for determination of the hydrochloride salts of fluoxetine, sertraline, and paroxetine in their pharmaceutical dosage forms. These methods were based on the reaction of the N-alkylvinylamine formed from the interaction of the free secondary amino group in the investigated drugs and acetaldehyde with each of 3 haloquinones, i.e., chloranil, bromanil, and 2,3-dichloronaphthoquinone, to give colored vinylamino-substituted quinones. The colored products obtained with chloranil, bromanil, and 2,3-dichloronaphthoquinone exhibit absorption maxima at 665, 655, and 580 nm, respectively. The factors affecting the reactions were studied and optimized. Under the optimum reaction conditions, linear relationships with good correlation coefficients (0.9986–0.9999) were found between the absorbances and the concentrations of the investigated drugs in the range of 4–120 μg/mL. The limits of detection for the assays ranged from 1.19 to 2.98 μg/mL. The precision values of the methods were satisfactory; the relative standard deviations were 0.56–1.24%. The proposed methods were successfully applied to the determination of the 3 drugs in pure and pharmaceutical dosage forms with good accuracy; the recoveries ranged from 99.1 to 101.3% with standard deviations of 1.15–1.92%. The results compared favorably with those of reported methods.

Precision Parameters of Methods of Analysis Required for Nutrition Labeling. Part I. Major Nutrients

1990 ◽  
Vol 73 (5) ◽  
pp. 661-680 ◽  
Author(s):  
William Horwitz ◽  
Richard Albert ◽  
Mike J Deutsch ◽  
Neville J Thompson
Keyword(s):  
Nutrition Labeling ◽  
Precision Data ◽  
Test Portion ◽  
Data Set ◽  
Strict Adherence ◽  
Methods Of Analysis ◽  
Relative Standard ◽  
Standard Deviations ◽  
Major Nutrients ◽  
Suitable Reference

Abstract Major components of foods and feeds are fat, protein, and carbohydrates. Fat and protein are determined by direct measurements that are Interpreted as the quantity of the constituent. Carbohydrates are usually calculated by difference. For this calculation, values for molsture/sollds, ash, and "fiber" are also needed. The readily available collaborative studies for the determination of these major components are reviewed In an attempt to assign precision parameters to validated methods of analysis. When a number of studies for the same analyte, In the same food, by the same method are available, It Is seen that the precision parameters among laboratories (standard deviations, SR; relative standard deviations, RSDR) and the ISO maximum tolerable difference functions (repeatability value, r; reproducibility value, R) are not characterized by any conventional distribution. The precision data are best summarized as a median or average parameter and the Interval containing the centermost 90% of reported values. Typically, the precision of methods of analysis can be expressed as a function of concentration only, independent of analyte, matrix, and method. The average RSDR value from each collaborative data set can then be used as the numerator In a ratio containing, as the denominator, the value calculated from the Horwitz equation: RSDR = 2 exp (1 — 0.5 log C) where C Is the concentration as a decimal fraction. A series of ratios consistently above 1, and especially above 2, probably Indicates that a method Is unacceptable with respect to precision. By this criterion, only the protein (KJeldahl) determination Is unqualifiedly acceptable with a 90% interval for RSDR of 1 to 3% at C values above about 0.01 (1 g/100 g). Fat, moisture/solids, and ash are acceptable down to limiting concentrations In the region of 1 to 5 g/100 g, If a test portion large enough to provide at least 50 mg of welghable residue or volatlles Is specified. Measurements of Individual carbohydrates and fiber-related analytes have unexpectedly poor precisions among laboratories. The variability, although high, may still be suitable for nutrition labeling. Reliability of analyses for the control of labeling of the primary nutrients must be achieved through quality assurance programs that require strict adherence to the directions of empirical methods and the use of suitable reference materials for absolute methods.

Precision Parameters of Methods of Analysis Required for Nutrition Labeling. Part II. Macro Elements—Calcium, Magnesium, Phosphorus, Potassium, Sodium, and Sulfur

1992 ◽  
Vol 75 (2) ◽  
pp. 227-239 ◽  
Author(s):  
William Horwitz ◽  
Richard Albert ◽  
Mike J Deutsch ◽  
Neville J Thompson
Keyword(s):  
Data Sets ◽  
Nutrition Labeling ◽  
Logarithmic Function ◽  
Potassium Sodium ◽  
Acceptable Limit ◽  
Decimal Fraction ◽  
Methods Of Analysis ◽  
Relative Standard ◽  
Calcium Magnesium ◽  
Standard Deviations

Abstract A previous paper reviewed the precision of analyses for the major macronutrients—fat, protein, and carbohydrates— as well as moisture/solids, ash, and "fiber." A similar review is now presented for the macro inorganic nutrients—calcium, magnesium, phosphorus, potassium, sodium, and sulfur. The precision parameters among laboratories (standard deviations, S; relative standard deviations, RSD; and repeatability, r, and reproducibility, R, values) are not characterized by any conventional distribution. The typical precision of the methods of analysis for these elements In food can be expressed solely as a logarithmic function of concentration, Independent of analyte, matrix, and method. The average RSDR value from each collaborative assay found in the literature Is used as the numerator in a ratio containing, as the denominator, the value calculated from the logarithmic function: RSDR(%) = 2( 1 -0.5 log C) where C Is the concentration as a decimal fraction. If this ratio, designated as HORRAT, Is above 2, the method Is probably unacceptable with respect to precision. About 20% of the 465 interlaboratory data sets studied for this paper show an RSDR exceeding the acceptable limit, with an overall average HORRAT of 1.2 at C ranging from about 20 x 10-6(20 ppm) to about 10-1 (10%). The variability, although high, may be acceptable for the purpose of nutrition labeling.

Performance Characteristics of Methods of Analysis Used for Regulatory Purposes.Part II. Pesticide Formulations

1991 ◽  
Vol 74 (5) ◽  
pp. 718-744 ◽  
Author(s):  
William Horwttz ◽  
Richard Albert
Keyword(s):  
Performance Characteristics ◽  
International Union ◽  
Method Performance ◽  
Applied Chemistry ◽  
The Past ◽  
Chromatographic Methods ◽  
Decimal Fraction ◽  
Collaborative Studies ◽  
Pesticide Formulations ◽  
Relative Standard

Abstract The precision parameters of the method-performance (collaborative) studies published In the AOAC Journal from 1915 through 1990 for pesticide formulations have been recalculated on a uniform basis by the International Union of Pure and Applied Chemistry 1987 protocol. About 93% of the 953 accepted assays, which are predominantly gravimetric (G), volumetric (V), and gas (GC) and liquid (LC) chromatographic methods, exhibit relative standard deviations among laboratories (RSDR) that are generally less than 2 times the values predicted from the Horwitz equation: RSDR (%) = 2 exp (1 - 0.5 log C), where C is the concentration expressed as a decimal fraction. UV, VIS, and IR spectrophotometrlc (S) methods are somewhat poorer, with about 80% of the reported RSDR values less than twice the predicted RSDR value. The precision parameters of pesticide formulations analyzed by the older methods (G, V, GC) are equivalent to those previously found for drug preparations in the same concentration range; the precision parameters of pesticide formulations analyzed by LC and S are somewhat poorer. Overall, however, the precision parameters of pesticide formulations are generally independent of analyte, method, and matrix, and are primarily a function of concentration. The method-acceptability decisions of the AOAC for pesticide formulations during the past 75 years can be approximated retrospectively by using a criterion for RSDR that is less than 2 times the RSDR calculated from the Horwitz equation.

Liquid Chromatographic Determination of Methyldopa and Methyldopa-Thiazide Combinations in Dosage Forms

1983 ◽  
Vol 66 (6) ◽  
pp. 1436-1442
Author(s):  
Susan Ting
Keyword(s):  
Acetic Acid ◽  
Mobile Phase ◽  
Chromatographic Determination ◽  
Dosage Forms ◽  
Reverse Phase ◽  
Relative Standard ◽  
Liquid Chromatographic Determination ◽  
Standard Deviations ◽  
Liquid Chromatographic

Abstract A liquid chromatographic (LC) method, using a reverse phase C18 column, an acetic acid-methanol-water mobile phase, and detection at 280 nm, was developed for the determination of methyldopa in tablets and oral suspensions and combinations of methyldopa with hydrochlorothiazide or chlorothiazide in tablets. A mixture of these 3 drugs was resolved in <8 min. Detector responses were linear for the following amounts (mg/mL) of drug injected: methyldopa 0.031-0.393, chlorothiazide 0.019-0.114, and hydrochlorothiazide 0.004-0.083. Recoveries from commercial dosage forms ranged from 99.1 to 100.9% for methyldopa, 99.2-100.4% for chlorothiazide, and 100.0-101.2% for hydrochlorothiazide. Replicate injections of methyldopa, chlorothiazide, and hydrochlorothiazide standard preparations alone or in combination gave overall relative standard deviations of <1.6% (n = 10). The results for methyldopa tablets by the proposed method were in agreement with those obtained by the USP XX method. The LC method detected as little as 0.6 μg 3-O-methylmethyldopa/mL and 0.5 μg 4-amino-6- chloro-l,3-benzenedisulfonamide/mL, which are sometimes found as contaminants of methyldopa and thiazides, respectively, and resolved methyldopa from its methyldopa glucose adduct, a substance found in methyldopa oral suspensions.

Precision Parameters of Standard Methods of Analysis for Dairy Products

1989 ◽  
Vol 72 (5) ◽  
pp. 784-806 ◽  
Author(s):  
James T Peeler ◽  
William Horwitz ◽  
Richard Albert
Keyword(s):  
Standard Deviation ◽  
Relative Standard Deviation ◽  
Freezing Point ◽  
Milk Products ◽  
Standard Methods ◽  
Methods Of Analysis ◽  
Collaborative Studies ◽  
Relative Standard ◽  
Repeatability And Reproducibility

Abstract The available collaborative studies for standard methods of analysis for various constituents of milk and milk products were examined in an attempt to assign specific repeatability and reproducibility precision parameters to these methods. The different collaborative assays for the primary constituents (moisture/solids, fat, protein), the nutritionally important elements (calcium, sodium, potassium, phosphorus), and miscellaneous analytes/physical constants (ash, lactose, salt, freezing point) produced different estimates of the precision parameters for the same method. A suitable summary of the precision estimates from collaborative studies is given by the reproducibility relative standard deviation, RSDR, which is relatively constant within a product and permits comparisons across products. An estimate of the variation of RSDR for an analyte from a number of collaborative studies is presented in terms of the median and 90% interval (the range of the centermost 90% of values). These estimates are only informative when a substantial number of independent studies are available for pooling the independent estimates to form a distribution of RSDR values. The RSDR for the determination of the primary constituents of milk and milk products is characterized by a median RSDR of 1% and a 90% interval of 0.3-3%, with RSDR estimates occasionally occurring below 0.3% and above 4%. These overall estimates appear to be independent of analyte, matrix, and method and apply to concentrations of primary constituents that range from about 2 to 80%. The repeatability relative standard deviation, RSDR, is unstable, although it tends to converge to about 0.5-0.7 X RSDR. Too few collaborative assays are available to characterize RSDR for the determination of certain other constituents (acidity, ash, lactose, salt, and the nutritionally important elements) unless RSDR values for different analytes, methods, and matrixes are pooled on the basis of similar analyte concentrations. When pooled, the RSDR values are generally better than predicted from the Horwitz equation, RSDR (%) = 2 exp (1—0.5 logioC), where C is the concentration expressed as a decimal fraction; all but one of 661 RSDR values are within the upper empirical limit of twice this curve.

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