Vol 69, No 5 (2020)

The paper considers pharmacopoeial approaches to the standardization of flavonoid-containing medicinal plant raw materials (MPRM) from different manufacturers in the Eurasian Economic Union (EAEU) countries. Two or three countries produce 31 names of MPRMs that are standardized according to the content of flavonoids. The breadth of use of this MPRM creates prerequisites for including these types in the common EAEU pharmacopeia. It is proposed to standardize a number of MPRM types, such as birch (Betula) leaves, black elder (Sambucusnigra) flowers, knotweed (Polygonumaviculare) herb, marjoram (Oreganum) herb, common horsetail (Equisetum arvense) herb, and beggarticks (Bidens) herb, according to the content of flavonoids, by using the unified chromatographic conditions for their determination by high performance liquid chromatography (HPLC). Using a new MPRM type (common heather (Calluna vulgaris) shoots) as an example, the authors consider the main stages of HPLC assay validation, by quantifying the amount of flavonoids in the plant materials, as calculated with reference to the analytical marker.

Introduction. To standardize the raw materials of ground burnut (Tribulus terrestris) herb, the authors have developed a procedure to measure the amount of flavonoids calculated with reference to rutin. To ensure that this procedure guarantees reliable and accurate test results, a technique is provided to validate the developed procedure. Objective: to validate a procedure for quantitative determination of the amount of flavonoids calculated with reference to rutin in the ground burnut herb, by using differential spectrophotometry. Material and methods. The procedure was validated on a combined sample of ground burnut herb. The validation parameters were determined using SF-2000 and SHIMADZU UV-1800 spectrophotometers. Results. The investigators established validation characteristics, such as linearity, precision (repeatability, reproducibility), and accuracy. Linearity was determined at five concentration levels. The correlation coefficient was 0.995, which indicates a linear relationship between the optical density and the total flavonoid content in extracts. The repeatability of the procedure was determined with tenfold replication under identical conditions within a short time interval. The intralaboratory reproducibility of the procedure was determined using three samples in triplicate. Its interlaboratory reproducibility was carried out on three samples in triplicate in two laboratories. The determination results confirmed the precision of the procedure under intralaboratory and interlaboratory reproducibility conditions, since the relative standard deviation did not exceed 15%. The accuracy of the procedure was established by adding the required amount of the standard to the extract. The results showed that the error in analysis was within the error in one determination and did not exceed 2.89%. Conclusion. The developed procedure is valid for the spectrophotometric determination of the sum of flavonoids calculated with reference to rutin in the ground burnut herb. The procedure requires no expensive reagents, is accurate, reproducible, and affordable, which allows it to be used for a reliable assessment of the quality of raw materials.

Introduction. Preferential drug provision programs had a significant impact on the development of the pharmaceutical market. They are a measure of social support for citizens of all age groups, who live in different subjects of the Russian Federation. The public authorities of the subjects of the Russian Federation have authority to organize the provision of certain categories of citizens with essential medicines (regional preferential drug provision programs (RPDPP)). An analysis of the indicators of RPDPP implementation for a number of years makes it possible to comparatively investigate the cost structure of drugs and to scientifically substantiate approaches to rationally spending the budget funds, to creating the program budget, and to predicting the future demand for medicines. Objective: to investigate the features of drug use by beneficiaries of regional responsibility as part of RPDPP implementation in case of the Samara Region. Materials and methods. The investigation object was data on the nomenclature of drugs dispensed to the population of the Samara Region as part of RPDPP implementation in the period 2014 to 2018. The investigators analyzed the structure of a drug assortment according to the amount of financial costs; the price characteristics of groups in accordance with the anatomical therapeutic chemical (ATC) classification; and the scope of using the prescribed drugs in natural and monetary terms. The investigation used techniques for comparative, retrospective, logical, graphical, and content analyses and a method for data grouping according to the ATC classification. Results. By using the Samara Region as an example, the investigators carried out a comparative analysis of the changes in the main RPDPP implementation indicators (funding amounts for the implementation of the program; the actual average drug acquisition cost per applying beneficiary; the average cost of one prescription; the structure of costs depending on the category of beneficiaries, etc.), which had occurred in 2014-2018. It was established that more than 50% of the RPDPP budget allocated for the purchase of drugs is spent on drugs that affected the digestive tract and metabolism (mainly drugs for the treatment of diabetes mellitus), antineoplastic agents, and immunomodulators. Synthetic antidiabetic medications, as well as antiasthmatic drugs constituted a significant portion of the consumption structure in natural terms within the RPDPP. Conclusion. The analysis of changes in the main indicators of implementing RPDPP in the Samara Region over 2014-2018 identified the most costly categories of diseases for the RPDPP budget. The results of this analysis can be used as the basis for the development of methodological recommendations for the rational spending of budgetary funds, the creation of the program budget, and the prediction of future demand for drugs.

Introduction. One of the main advantages of studying human hair over biofluids is that hair analysis allows one to determine the time course of changes in the use of psychoactive substances over several weeks, months, and even years. The role of testing the hair as an alternative, complementary human biomatrix has expanded across the spectrum of toxicological studies. Objective: to identify the possibility of determining the limitation period for taking a drug substance on hair samples from laboratory animals after discontinuing the drug. Material and methods. Phenobarbital and diphenhydramine were model drug substances (MDSs). The investigation was conducted using an Agilent 7890 A/5977 MSD GC/MS sampler. The experiments were done on laboratory animals (red and black male guinea pigs). Hair samples were prepared using the enzymes chymopsin, chymotrypsin, trypsin, and papain. Results. MDSs were detected in the urine of laboratory animals within 12 (phenobarbital) and 4 (diphenhydramine) days after their administration. These substances were found in the hair on 42 days of the experiment after the sample being prepared using the authors' procedure for enzymatic hydrolysis with the above proteases. Phenobarbital was seen in the amounts comparable to those in the chronic use of the substance, whereas the amount of diphenhydramine was 3-4 times lower than that in chronic intoxication. These results were consistent with the pharmacokinetic characteristics of the substances, with their half-lives and the features of their metabolism. It should be noted that or phenobarbital and diphenhydramine, the amount of the substance detected after 42 days to be greater for red hair than for black one. Conclusion. The procedure for hair sample preparation by enzymatic hydrolysis in combination with GC-MS analysis makes it possible to detect substances in the human biological object, even after urine and blood tests yield negative results. However, the high determination error makes it impossible to quantify.