The discriminatory ability of analytical quality control test methods : a comparison of test results from different international monographs of quinine sulfate tablets
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Malaria is a parasitic disease claiming one million lives worldwide annually. Unfortunately, malaria-endemic countries in need of good quality medicines are also overwhelmed with counterfeit or substandard medicine. This results in treatment inefficacy, resistance towards treatment and death. Counterfeit or substandard quinine sulfate tablets are known to have infiltrated the market, however at this point in time, treatment efficacy of quinine sulfate has fortunately not yet been significantly impaired by resistance, but immediate action is required to prevent it from becoming obsolete. Validated analytical methods with justified specifications are effective in controlling the quality of medicines and to minimise the effect of poor quality medicines. Pharmacopoeia specifies analytical quality control procedures and accompanying specifications to standardise acceptable levels of product quality. Understandably, different monographs of different pharmacopoeias are developed by different independent laboratories and therefore their respective test procedures/specifications for the same FPP may differ from each other. Institutions such as the Pharmacopoeial Dicussion Group (PDG) aim to harmonise pharmacopoeia in order to synchronise final outcomes. This study evaluated the relevancy of differences in analytical procedures, results and specifications for quinine sulfate tablets set by the United States Pharmacopoeia (USP), British Pharmacopoeia (BP) and International Pharmacopoeia (Ph.Int.) in an aim to ensure that these different methods all provide with similar final outcomes and that they be effective in successfully evaluating the quality of quinine sulfate tablets. Four quinine sulfate tablet products were obtained from different manufacturers and were subjected to the tests of all three pharmacopoeia – BP, USP and Ph.Int. The results from identification, assay and related substance testing concluded that the outcomes were the same between the pharmacopoeia despite their differences in techniques/procedures/specifications. The assay, identification and related substances methods and specifications set by each respective monograph were deemed appropriate to evaluate the quality of quinine sulfate tablets. Even with differences in methodology, quantitative techniques and specifications, the USP and BP dissolution methods for quinine sulfate tablets shared the same final outcome at the first stage of dissolution, whereas none of the products achieved a compliant outcome using the Ph.Int. dissolution method. Possible reasons for the poor dissolution (when using the Ph.Int. method) were identified and investigated. Investigation into the solubility of quinine sulfate found the Ph.Int. dissolution method conditions to be too stringent, as the solubility of quinine sulfate in phosphate buffer pH 6.8 (dissolution medium specified by the Ph.Int.) was found to be much less than in acidic media (as proposed by the BP and USP dissolution methods). Several adapted dissolution methods (called developmental studies) were investigated to serve as potential alternatives for the Ph.Int. dissolution method. The developmental studies investigated an alternative dissolution medium, agitation rates (50 rpm, 75 rpm, 100 rpm) and medium volumes (500 ml, 750 ml, 900 ml and 1000 ml). Developmental study 6 was proposed as an alternative dissolution method. Developmental study 6 stipulates the use of the same medium as the original Ph.Int. method, as it was deemed the medium of choice for its discriminatory ability. To address the impaired solubility of quinine sulfate in phosphate buffer, the medium volume and agitation were increased (in reference to the original method) to 900 ml and 100 rpm respectively. The same analytical quantitation technique (UV-Vis spectroscopy) is proposed for Developmental study 6. The newly proposed method provided with final outcomes comparable to that of the USP and BP, however having more discriminatory power than the USP and BP.
- Health Sciences