Purity test results

When close control of purity is essential it may be necessary to assemble the test specimens in a dry box under an inert atmosphere and to weld the containers shut under inert gas or vacuum before placing on test. With some environments even the small amount of oxygen and moisture adsorbed on the component surfaces will significantly affect the test results. In one laboratory this problem was eliminated by maintaining within the dry box a container of molten sodium at 250°C —a rather cumbersome procedure, but one which emphasises again the importance of purity. 

Evaluation of loop-test results Although the thermal loop test approximates to the conditions which obtain in a dynamic heat-transfer system, in evaluating the results it is necessary to be aware of those aspects in which the test differs from the full-scale unit, as otherwise unwarranted confidence may be placed in the data. Assuming that adequate attention has been paid to the purity and condition of components, etc., the following factors will, according to ASTM G68 1980, influence the observed corrosion behaviour ... 

If reference materials are not available, the challenge study lives np to its name. Specificity may still be demonstrated by a comparison of test results containing the impurities of interest to a second, well-characterized procedure (e.g., USP method). If a secondary method is unavailable, peak purity evaluation may be used to further demonstrate specificity of the method. 

Table 1. Experimental conditions and tests results of purity of benzene crystal...

Tests to establish the identity, strength, and purity of the test and control articles need not comply strictly with GLP requirements (e.g., protocol, QAU inspection requirements), but good documentation of anal5dical test results (usually in a laboratory notebook) and retention of raw data for such tests is a good practice. As the development process proceeds and the same material is used in both nonclinical and clinical studies, CGMP principles wiU apply to the production and characterization processes. 

When impurities or degradation products are unidentihed or unavailable, selectivity may be demonstrated by analysis by the method in question of samples containing impurities or degradation products and comparing the results to those from additional purity assays. The degree of agreement of test results is a measure of the selectivity. 

Sensitivity to Heat and Electric Charge The Ignition (or Explosion) Temperature Test measures thermal stability, which is discussed under Chemical Properties . The test is run with the sample either confined or unconfined (see Vol 1, XVI). Test results are quite sensitive to conditions and to sample purity, and as a result, ignition values for TNT reported in the literature differ by as much as 200° C (Ref 156 see discussion in Vol 4, D583-L ff). Careful studies using different procedures with confined samples have given ignition temps of 275° (Ref 156),... 

Lot-to-lot differences in the purity of the therapeutic agent must be considered when evaluating in-process and finished-product test results. In addition to potency such qualities as particle size distribution, bulk density, and source of the material will be of interest. Such information should be available from the raw material test reports prepared by the quality control laboratory for each lot of material received. The physical characteristics of the excipients should not be overlooked, especially for those materials with inherent variability. Metallic stearates is a classic example. In such instances, the source of supply is desirable information to have available. 

Several field test studies have been undertaken utilizing the SEPAREX process in a 2-in. diameter element size Due to the modular configuration of membrane systems, a full size system can be directly designed from the test results with a small pilot plant. Although the flow rates for a pilot unit are considerably lower than might be encountered in a full-size system, all process parameters such as product purities, pressure drop, product recoveries, optimum pressure and temperature, membrane area required and series/parallel arrangement of the elements can be directly determined. 

Test results at 25°C and 90°C have been interpreted at Pennsylvania State University as follows. The higher the purity of the Zr02, the more likely it is to behave well as a pH sensor. Exceptions to this rule are titanium, which is beneficial for thermal shock resistance, and yttria, which is necessary for polymorphic stabilization. The optimum Y20, content was investigated by testing Zr02 tubes with Y203 contents of 4, 6, 8, 10, and 12 mol%. 

Developmental effects were reported in one study in which female rats were treated orally during conception and pregnancy with approximately 18.3 mg barium/kg/day as barium carbonate (Tarasenko et al. 1977). Reported effects in offspring included increased mortality, increased leukocyte count, disturbances in liver function, and increased urinary excretion of hippuric acid. The later study is inadequate for evaluating developmental effects of oral barium exposure because of major study limitations. These limitations include a general lack of information provided by the authors regarding experimental methods, exposure conditions, and test results, and no information as to the number of animals tested, the purity of the test material, the statistical methods used, and whether or not controls were used. No other animal studies evaluating developmental effects were available. 

For all analytical methods the quality of the results ultimately relates back to the chemical purity of the very best available SRM and to the linearity of the correlation curve for the experimentally measured property vs. the SRM concentration. For substances that are naturally chiral there is the additional very serious concern about enantiomeric purity. The determination of an enantiomer whether for an enantiomeric purity test, or for an enantiomeric ratio or excess test in the study of a partial racemic mixture, is one of the more difficult analytical problems. To actually report the enantiomeric purity of an enantiomer as better than 99% is truly beyond the capability of current analytical methodology [31], for after all few substances ever have a chemical purity that is guaranteed to be greater than 99%. So, as mentioned earlier, one has to accept the fact that the results are measured relative to an enantiopurity of an SRM that is defined to be 100%. This limitation of course impacts on the true meaning of a calculated enantioexcess, and to a much lesser degree perhaps, in assays of chiral substances extracted from plant materials using calibration data that were obtained for synthetic SRM s. 

The specificity of the method was checked with a peak purity test of the assay preparation performed with a photodiode array detector. The peak purity values for metformin and glibenclamide were observed to be 995 and 999, respectively. The results of the peak purity analysis show that the peaks of the analytes were pure and that the formulation excipients did not interfere with the analyte peaks. 

Specifications for the finished product Two specifications at release and end of shelf-life List general characteristics, specific standards tests and limits for results for the finished product must be provided Analytical test procedures described (physicochemical properties, identity of API) Quantitative determination of active, deviations, purity tests, pharmaceutical tests, colouring antimicrobial or chemical preservatives, results of validation studies, comments on the choice of routine tests and standards provided Copy of pharmacopoeia monograph and verification data Results of batch analysis (inc. date of manufacture, place of manufacture, batch size and use of batch tested) ... 

The primary objective of method validation is to provide a high degree of assurance that the specified method consistently provides accurate test results that evaluate a product against its defined specification and quality attributes (Chapter 12). The regulations require that validation data be available to establish that the analytical procedures used in testing meet proper standards of accuracy and reliability. All analytical procedures require some form of validation, regardless of whether the method is used for stability, in-process analysis, release, or acceptance. Most of the discussions focus on the validation of HPLC methods using assay and purity determinations nevertheless, fundamentals of the approach can be applied to most method validation activities. 

For each herbal drug preparation, a comprehensive specification must be submitted. This must be established on the basis of recent scientific data and must give particulars of the characteristics, identification tests, and purity tests. This has to be done, for example, by the appropriate chromatographic methods. If deemed necessary by the results of the analysis of the starting material, tests on microbiological quality, residues of pesticides, fumigation agents, solvents, and toxic metals have to be carried out. Radioactivity should be tested if there are reasons for concerns. Quantitative determination (assay) of markers or of substances with known therapeutic activity is required. The content must be indicated with the lowest possible tolerance. The test methods must be described in detail. 

The use of reaction sequences is also common in the analysis of pharmaceuticals. For example, for the purity test for hydrochlorothiazide (HCT) the DAB specifies a nitration reaction followed by reaction with naphthylethylenediamine dihydrochloride, in which the reaction sequence is performed as in the example given below. HCT is a diuretic which is often used in combination with beta-blockers for the treatment of hypertension (high blood pressure). Diuretics of this type are also abused in sport (doping) and appear on the list of banned substances prepared by the IOC (International Olympic Committee). In the quantitative determination of HCT in urine, the red azo dyes formed in the derivatization (parent substance and metabohtes) is regarded as a doping-positive result [111]. The complete specification for this analytical method, known as Application A-43.2, can be obtained from CAM AG. 

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