Performance characteristics of methods of analysis used for regulatory purposes. I. Drug dosage forms. C. Automated methods

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 (RSDo) and among-laboratories (RSDx) were 1.1 and 1.9%, respectively, and the ratio of RSDo/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. E. miscellaneous methods

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, RSDo) for the instrumental methods was 1.5%; the reproducibility relative standard deviation (among-laboratories, including within-, RSDx) was 2.6%; the ratio RSDo/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

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

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 RSDo/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.     

Performance characteristics of methods of analysis used for regulatory purposes. Part II. Pesticide formulations.

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 spectrophotometric (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.     

Equivalence of microbiological and hydroxylamine methods of analysis for ampicillin dosage forms.

Ampicillin formulations were assayed by microbiological and hydroxylamine methods to determine whether thehydroxylamine analytical method is a suitable substitute for the microbiological method. Paired assay results by the 2 analytical methods were obtained on different strengths of tablet, capsule, and suspension, formulations containing ampicillin and ampicillin degradation compounds. Several statistical tests were used to assess the equivalence of the paired assay results. The data analyses indicate that the hydroxylamine method is a suitable substitute for the microbiological method for potency assays and stability studies of ampicillin formulations. The hydroxylamine method yielded slightly higher assay results than the microbiological method for severely degraded formulations.     

Column chromatographic analysis of barbiturates in their dosage forms. IV. Combinations with parabens.

The nature of the alkaline hydrolysis of some barbiturates in combinations with parabens (p-hydroxybenzoates) was studied with controlled variables, including temperature, viscosity, and concentrations of sodium hydroxide, barbiturate, and parabens. The kinetic studies showed that parabens could be completely hydrolyzed in strong base at 40 degrees C in 1 hr, while the barbiturate remained intact and was readily isolated by partition chromatography, Based on the theoretical results, a partition chromatographic procedure for butabarbital with parabens was devised. Standard recoveries averaged 100.7% with a standard deviation of 0.89. Kinetic data indicate that the hydrolysis of parabens could also be applied to analyze combinations with amo-, seco-, and pentobarbitals. Phenobarbital and parabens are readily separated by partition chromatographic methods without prior hydrolysis of the parabens. The low extraction constant for phenobarbital allowed its retention on a column against relatively strong solvents while the intact parabens are eluted. A slightly modified method was applied to the separation of phenobarbital from parabens. Standard recoveries average 99.9% with a standard deviation of 0.69.     

Analysis of pharmaceutical dosage forms for oxfendazole: I. Reverse phase liquid chromatographic determination of oxfendazole in swine premix

A reverse phase liquid chromatographic (LC) procedure is described for quantitating oxfendazole (2-(methoxycarbonylamino)-5-phenylsulfinylbenzimidazole] in swine premix. Sample preparation consists of extracting oxfendazole with an acetone-methanol mixture. An aliquot of the extract is then centrifuged to separate undissolved premix excipients. Internal standard is added to the supernate and the sample is further diluted with water-acetonitrile-phosphoric acid (80 + 20 + 1). Oxfendazole is quantitatively determined using a Partisil-5-ODS-3 column with acetonitrile-0.01 M phosphate buffer (pH 6.0) as the mobile phase. The method is stability specific and yields a mean recovery of 101.1 +/- 0.4% for the 1.35% premix formulation. The dependence of chromatographic performance characteristics on mobile phase organic content, pH, and buffer concentration is also reported.     

Column chromatographic analysis of barbiturates in their dosage forms. II. secobarbital, amobarbital, and pentobarbital.

A general method for the analysis of barbiturates, using column parition chromatography, was extended to the assay of secobarbital, amobarbital, and pentobarbital. A solution of the barbiturate constitutes the immobile phase in the chromatographic system. It is eluted with ether-isooctane (1+9) and passed onto a K3PO4 column, which retains the barbiturate while extraneous materials are washed out. The barbiturate is removed from the column with etherisooctane (3+1), extracted from the eluate with NH3, and measured spectrophotometrically.     

Precision parameters of methods of analysis required for nutrition labeling. Part I. Major nutrients

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 moisture/solids, 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 weighable residue or volatiles 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.     

An assessment of the Fosberg and Ellenberg methods of classifying vegetation for conservation purposes

This paper describes a field trial of two rapid-survey methods of classifying vegetation for conservation purposes. The work was carried out by staff and students of the Conservation Course at University College, London, on Majorca in the spring of 1971. A brief review of the two methods is followed by an account of the difficulties encountered with their use in the field and of their theoretical advantages and disadvantages. It was concluded that both methods offer a quick, repeatable approach to vegetation classification which requires little previous knowledge. Fosberg's method was considered the more logical because Ellenberg's includes habitat data which may lead to circularity of argument. Ellenberg's was found to be the easier to use in the field, but this is possibly because it has been principally developed in temperate regions. Both methods offer a very useful framework for an ecological inventory of an area but are subject to practical difficulties when the vegetation has to be mapped.     

Liquid chromatographic method for perphenazine and its sulfoxide in pharmaceutical dosage forms for determination of stability

A liquid chromatographic method is described for determination of perphenazine and perphenazine sulfoxide in representative dosage forms. Sulfoxide levels were nondetectable or less than 1% in tablets and in an injectable product. Sulfoxide levels increase with time in some syrup formulations and may be as high as 11% in syrup formulations before their expiration date.     

Analysis of pharmaceutical dosage forms for oxfendazole: II. Simultaneous liquid chromatographic determination of oxfendazole and trichlorfon in equine paste

A reverse phase liquid chromatographic procedure is described for the simultaneous determination of oxfendazole [2-(methoxycarbonylamino)-5-phenylsulfinylbenzimidazole] and trichlorfon [(2,2,2-trichloro-1-hydroxyethyl)phosphonic acid dimethyl ester] in equine paste. The sample is extracted by sonication in methanol. Insoluble excipients are removed by centrifugation and an aliquot plus internal standard are diluted with dilution solvent (water-acetonitrile-phosphoric acid, 80 + 20 + 1). The samples are filtered and injected onto a Partisil-5 ODS-3 column with acetonitrile-0.01 M phosphate buffer pH 6.0 (20 + 80) as mobile phase. Method specificity is confirmed using an absorbance rationing technique. The method yields mean recoveries of 100.9 and 100.0% for trichlorfon and oxfendazole, respectively. Dependence of chromatographic performance characteristics on mobile phase organic content, pH, and buffer concentration is also reported.     

固体废弃物及土壤中磷的形态分析技术

畜禽粪便等固体废弃物及土壤中磷的形态分析对于管理固体废弃物、提高磷素利用率、减少磷素流失风险具有重要意义。自20世纪初以来,已提出多种固体废弃物及土壤中磷素形态分析的方法,包括化学分级、酶水解法、X射线衍射(XRD)、红外光谱(FT-IR)3、1P核磁共振(31P NMR)、X射线吸收近边结构(XANES)等。本文系统总结了一些固体废弃物及土壤中磷素形态分析的方法,比较了其特点,指出只靠单一的方法并不能很好地鉴定固体废弃物及土壤中磷素的形态,必须综合考虑运用多种方法,从而为磷素形态分析提供方法选择的依据,同时为进一步发展固体废弃物及土壤中磷素形态分析新技术奠定基础。     

直播方式对水稻生理性状和产量的影响及其成本分析

为探讨水稻不同直播方式对产量和生理特性以及成本的影响,该文设置了旱直播、水直播和机条播3种直播方式,研究了水稻的产量表现、群体发育、生理特征以及经济效益。结果表明,与旱直播相比,机条播和水直播的产量分别增加了11.9%和6.3%,氮肥农学利用率分别增加了10.1%和4.9%。从产量构成因素分析,产量的提高主要得益于单位面积穗数的增多。机条播显著提高了茎蘖成穗率、花后与成熟期干物质积累量、生长中后期的茎蘖数、叶面积指数与持续期、群体生长速率、叶片光合速率和根系氧化力。机条播因其机械作业效率高、费用低以及除草成本低使得总成本降低和经济效益提高,说明机条播方式提高了直播水稻叶片光合性能,并促进了地上部群体合理生长和地下部根系活力,从而获得了较高的产量和经济效益。     

High pressure liquid chromatographic separation and identification of vitamins D2 and D3 in the presence of fat-soluble vitamins in dosage forms.

A simple and rapid qualitative method is described for determining the presence of vitamin D2 (ergocalciferol) and/or vitamin D3 (cholecalciferol) in various preparations by reverse phase high pressure liquid chromatography (HPLC). When both D2 and D3 are present, this method effectively separates and identifies each vitamin D form by its respective retention time. A significant difference between vitamins D2 and D3 exists in their antirachitic activity in poultry. Preparations can be tested rapidly by this method to ascertain that the correct D vitamin form has been added. Fat-soluble vitamins such as vitamins A, E, K1, and K3 do not interfere. Vitamins D2 and D3 were separated at the baseline in model preparations. As little as 2 ng each of vitamin D2 and vitamin D3 can be separated and identified.