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DOI: 10.18413/2658-6533-2019-5-2-0-7

Practical aspects of the analysis of pharmaceutical substances by the indicator «bacterial endotoxins»

Background:Safety is one of the basic medicine requirements. «Bacterial endotoxins» is the most important safety indicator of parenteral drug products, ensuring their proper quality. The use of the LAL test to determine bacterial endotoxins allows us to normalize the content of impurities which cause a pyrogenic reaction for patients. The evaluation of this indicator is carried out according to the requirements of the general pharmacopoeial article (OFS 1.2.4.0006.15) «Bacterial endotoxins» of the State Pharmacopoeia of the GF XIII, where general methodological information is given for performing the analysis of medicines according to the indicator «Bacterial endotoxins». There are no detailed recommendations in the OFS including the conditions for sample preparation, which are significant in the performance of the LAL test, especially for pharmaceutical substances. This greatly complicates the procedure for determining bacterial endotoxins, especially when the substances are water-insoluble or interfere with the enzymatic reaction of bacterial endotoxins with LAL reagents. The aim of the study:To consider the main steps that can influence the obtaining of a reliable assessment of their quality at the stage of development of methods for determining bacterial endotoxins in pharmaceutical substances. Materials and methods:The study subjects are pharmaceutical substances of daunorubicin hydrochloride, calcium chloride hexahydrate, citric acid (monohydrate), oxaliplatin, rifampicin and streptomycin sulfate. To carry out the LAL test, in the gel-thrombus modification, we used: a LAL reagent with a sensitivity of 0,03 EU / ml (where EU is an endotoxin unit), control standard endotoxin corresponding to the reagent, water for the LAL test, tris buffer (Tris-hydroxymethylaminomethane hydrochloride), ethyl alcohol 96%. Results:Methods for the determination of bacterial endotoxins for six pharmaceutical substances have been improved: the theoretical limit value of bacterial endotoxins has been theoretically calculated and experimentally tested. Conclusion:The process of sample preparation of pharmaceutical substances has been optimized and the procedure for eliminating the influence of interfering factors on the results of the LAL test has been developed

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