Establishing new acceptance limits for dissolution performance verification of USPC apparatus 1 and 2 using USPC prednisone tablets reference standard.

PURPOSE: On 1 March 2010, the US Pharmacopeial Convention released into commerce Lot P1I300 of its Prednisone Tablets Reference Standard for use in periodic performance verification testing (PVT) of dissolution Apparatus 1 and 2. This report presents the collaborative study data, development of the acceptance limits, and results from supporting work for this Lot. METHODS: The collaborative study involved 25 collaborators who provided data for Apparatus 1 and 31 who provided data for Apparatus 2. These limits are for the geometric mean and percent coefficient of variation (%CV) instead of per-individual results as for prior lots. Stability of results and sensitivity to test performance parameters were also studied. RESULTS: To determine new PVT acceptance limits, the authors calculated geometric mean and variance components as percent coefficient of variation. The move to the geometric mean and %CV criteria brings the acceptance criteria in line with current accepted statistics and provides a more realistic assessment of the system's performance. Results for Apparatus 1 are stable over time, but for Apparatus 2, the mean decreases over time. Acceptance criteria are adjusted for this trend. Lot P1 demonstrates sensitivity to test performance parameters (vessels and degassing). CONCLUSIONS: Apparatus 1 results are stable over time. Those in Apparatus 2 show a decrease over time in the geometric mean but show no trend in variability. The current tablets are shown to remain sensitive to two operational parameters, degassing and vessel dimensions, not covered by mechanical calibration. The new acceptance limits for Lot P1 are based on geometric mean and %CV for Prednisone Tablets Reference Standard Lot P1I300. The limits better control variability than the prior per-individual-result limits.

Measurement science for food and drug monographs: toward a global system.

This article continues USP's public dialogs about applications of modern measurement science (metrology) to public or private specifications (monographs) of food and drug articles. An objective of the discussion is to promote understanding of traceability and uncertainty of measurement results. Adoption of modern metrologic principles helps ensure that a measurement of one or more property values (attributes) of a food or drug article are acceptable without regard to when (time), where (space), or how (technology) the measurement was conducted. The approach is applicable to both in-process and end-product measurements and facilitates and supports understanding of manufacturing and measurement variability relative to acceptance criteria. Application of modern metrologic principles to measurement of food and drug articles expands opportunities to ensure availability of good quality food and drugs in national and international markets.

Change in criteria for USP dissolution performance verification tests.

The US Pharmacopeial Convention has been evaluating its performance verification tests (PVT) for several years. These tests help ensure the integrity of the US Pharmacopeia performance test when a dissolution procedure, as described in General Chapter Dissolution <711>, is relied upon to test a nonsolution orally administered dosage form. One result of the evaluation is a change in the PVT criterion from one based on individual tablet results to one based on the mean and variability of a set of tablets. This paper describes the new PVT and its criterion and how its acceptance limits are derived from results of a collaborative study, explains a two-stage option for the test, and presents operating characteristics.

Effect of Variables on pH Measurement in Acid-Rain-Like Solutions as Determined by Ruggedness Tests.

Ruggedness Test (RT) experiments were performed to assess the significance of the various main factors which affect pH measurements in low ionic strength aqueous solutions, as well as to establish the presence of interactions between the main factors. Stirring has an adverse effect on the measurement of pH, since it not only increases the random noise but also biases the measured value. Temperature control to the nearest 0.5 °C is sufficient for maintaining measurements accurate to 0.01 pH. Addition of NaNO3 or KCl can not be tolerated in accurate pH measurements. Three small two-factor interactions were also revealed.

Ruggedness Testing-Part I: Ignoring Interactions.

A straightforward explanation of the statistical technique of ruggedness testing is presented. Efficient Plackett-Burman designs are used in ruggedness tests. These designs involve the simultaneous change of levels of a number of variables. The designs allow the ruggedness test user to determine the effect of the separated variables on the measurement process. This paper (Part I) deals with the common situation where two-factor and higher order interactions can be safely ignored. A method is presented for evaluating the experimental uncertainties. A detailed example of glass electrode measurements of pH of dilute HCl solutions is used to illustrate ruggedness testing procedures.

Development of a Standard Reference Material for Rainwater Analysis.

This paper describes the development of Standard Reference Material, SRM 2694, "Simulated Rainwater," intended to aid in the analysis of acidic rainfall. Details of the formulation and preparation of the two levels of solutions (2694-I and 2694-II) are given. The 10 analytical techniques used to measure the 12 components in the solutions are described in brief. The data used in the statistical evaluation of the results are summarized and the recommended values for pH, specific conductance, acidity, fluoride, chloride, nitrate, sulfate, sodium, potassium, ammonium, calcium, and magnesium are tabulated. The instability of ammonium ion in acidic solutions is discussed. Recommendations for the use of SRM 2694, particularly with regard to the measurement of pH, are given.

Ruggedness Testing-Part II: Recognizing Interactions.

This paper is a continuation of the preceding article which introduced the reader to the general concepts of ruggedness testing. The current paper describes the effects of interactions on the measurement process, and presents procedures for the separation of the main effects from the two-factor interactions. The general characteristics of interactions are described in some detail. A short-cut procedure is presented for the calculations. A number of examples of glass electrode measurements of pH of dilute acid solutions are used to illustrate ruggedness testing procedures.

An Interlaboratory Test of pH Measurements in Rainwater.

An interlaboratory test of pH measurements in rainwater has been conducted. Various types of electrodes and junction materials were used in this test. The results of this exercise verify that there are significant differences in the pH values of low ionic strength solutions reported by various laboratories. Other work suggests that these differences are due to residual liquid junction potentials. Furthermore, this test confirms the efficacy of using dilute solutions of a strong acid as working standards for pH measurements in acid deposition studies.

High Precision Coulometric Titration of Uranium.

An improved method tor the coulometric assay of uranium and uranium oxide has been developed based on the electrogeneration of Ti(III) in H2SO4, using Fe(II) as a catalyst. The endpoint is determined amperometrically. Hydrogen peroxide is used as the oxidant in the dissolution of the uranium to avoid interferences from nitrate. The precision of the method as indicated by the standard deviation of an individual observation ranged from 0.008 weight percent for the analysis of the metal to 0.02 weight percent for the analysis of the oxides.

The Determination of Trace Levels of Cyanide by Ion Chromatography with Electrochemical Detection.

An improved method for the determination of trace quantities of free cyanide has been developed using ion chromatography with electrochemical detection. Detection limits of 1 µg/L have been achieved with linearity of response over the range 1 to 1000 µg/L. The precision of replicate injections is 0.6 percent, expressed as the relative standard deviation. The method has been applied to the analysis of dust samples.

Sample Preparation in Ion-chromatography.

Ion-chromatography, a relatively new technique in analytical chemistry, has already shown great promise toward solving complex trace analysis problems, in particular the speciation and quantitation of anions. It is especially attractive to the field of microanalysis. The method of sample preparation, however, is crucial in order to realize this capacity. Existing microanalytical methods nearly always must be modified to be compatible with ion-chrornatography, and often, more extensive sample cleanup is required than is needed for "single species" methods. These considerations have been applied to the determination of chloride and bromide in waste oil, and to the analysis of oyster tissue. Pretreatment with polystyrene resin and ion-exchange resin is discussed.