Sustainable Stability-Indicating spectra manipulations for the concurrent quantification of a novel Anti-COVID-19 drug and its active Metabolite: Green profile assessment.

Millions of individuals have lost their lives and changed their routines as a direct consequence of exposure to the coronavirus (Covid-19). Molnupiravir (MOL) is an orally bioavailable tiny molecule antiviral prodrug that is effective for curing the coronavirus that produces serious acute respiratory disorder (SARS-CoV-2). Fully green-assessed stability-indicating simple spectrophotometric methods have been developed and fully validated as per ICH criteria. The potential impact of degradation products of drug components on the safety and efficacy of a medication's shelf life is likely to be negligible. The field of pharmaceutical analysis necessitates various stability testing under different conditions. The conduct of such inquiries affords the prospect of predicting the most probable routes of degradation and ascertaining the inherent stability characteristics of the active drugs. Consequently, a surge in demand arose for the creation of an analytical methodology that could consistently measure the degradation products and/or impurities that may be present in pharmaceuticals. Herein, five smart and simple spectrophotometric data manipulation techniques have been produced for the concurrent estimation of MOL and its active metabolite as its possible acid degradation product namely; N-hydroxycytidine (NHC). Structure confirmation of NHC build-up through IR, MS and NMR analyses. All current techniques verified linearity ranging from 10 to 150 µg/ml and 10-60 µg/ml for MOL and NHC, respectively. The limit of quantitation (LOQ) values were in the range of 4.21-9.59 µg/ml, while the limit of detection (LOD) values were ranging from 1.38 - 3.16 µg/ml. The current methods were evaluated in terms of greenness by four assessing methods and confirmed to be green. The significant novelty of these methods depends on their being the first environmentally soundness stability-indicating spectrophotometric approaches for the concurrent estimation of MOL and its active metabolite, NHC. Also, the preparation of purified NHC delivers significant cost savings, instead of purchasing an expensive ingredient. These smart methods were utilized for analyzing the pharmaceutical dosage form which may be of great benefit to the pharmaceutical market.

DEVELOPMENT OF CONDITIONS FOR ANALYTICAL DIAGNOSIS OF POISONING WITH CLOPIDOGREL.

Introduction. Clopidogrel bisulfate (Clopidogrel) is one of the main drugs for the treatment of various cardiovascular diseases (acute coronary syndrome, ischemic stroke, transient ischemic attack, peripheral artery disease, etc.). Especially, this drug is very relevant in the treatment of COVID-19. Clopidogrel has repeatedly been the cause of lethal poisoning, and cases of clopidogrel being used for suicide are very common in China. According to the studied literature data, the analysis of this drug in the biological material is not presented. Objective: The aim of the research was to establish the distinctive ability of conventional methods of isolating medicinal substances from biological material in relation to clopidogrel in chemical and toxicological analysis (CTA). Material and methods. The study was carried out with model samples of pig liver that had not undergone putrefactive changes, which contained the studied drug. Detection and quantification of clopidogrel in extracts were carried out using thin-layer chromatography (TLC) and UV spectrophotometry. Results. The isolation efficiency of clopidogrel according to the method of A.A. Vasilyeva was 57.75±5.08%, according to the method of V.P. Kramarenko – 64.23±5.44%. When using the isolation method of A.A. Vasilyeva, the detection limit of clopidogrel was 1.04%, according to the method of V.P. Kramarenko – 1.09%. The limit of quantitative determination of clopidogrel according to the method of A.A. Vasilyeva is 3.31%, according to the method of V.P. Kramarenko – 3.34%, respectively. Conclusion. For analytical diagnostics in case of clopidogrel poisoning, TLC screening and UV spectrophotometric determination must be carried out with preliminary TLC purification. Isolation of clopidogrel with water acidified with ethyl alcohol (the Stas-Otto method) does not work. The effectiveness of isolating the drug by the method of V.P. Kramarenko is 64.23±5.44%. The greatest selectivity of the UV spectrophotometric method for determining clopidogrel in biological material in relation to matrix components was provided by the method of isolation with water acidified with sulfuric acid (V.P. Kramarenko's method). (English) [ FROM AUTHOR] Введение. Клопидогрела бисульфат (клопидогрел) является одним из основных лекарственных препаратов для лечения различных сердечно-сосудистых заболеваний (острый коронарный синдром, ишемический инсульт, транзиторная ишемическая атака, заболевания переферических артерий и др.). Данный препарат особенно актуален при лечении СОVID-19. Неоднократно клопидогрел был причиной летальных отравлений, например, в Китае очень часто встречаются случаи использования клопидо- грела в целях самоубийства. Анализа данного препарата в биологическом материале по литературным данным не представлено. Целью исследований явилось установление отличительной способности клопидогрела, общепринятой в химико-токсико- логическом анализе методов изолирования лекарственных веществ из биологического материала. Материал и методы. Исследование проводили с модельными пробами свиной печени, не претерпевшей гнилостных изме- нений, которые содержали исследуемый препарат. Обнаружение и количественное определение клопидогрела в экстрактах проводили с помощью тонкослойной хроматографии (ТСХ) и УФ-спектрофотометрии. Результаты. Эффективность изолирования клопидогрела по методу А.А. Васильевой составила 57,75±5,08%, по методу В.П. Крамаренко – 64,23±5,44%. При использовании метода изолирования А.А. Васильевой предел обнаружения клопидогрела составлял 1,04%, по методу В.П. Крамаренко – 1,09%. Предел количественного определения клопидогрела по методу А.А. Васильевой – 3,31%, по методу В.П. Крамаренко – 3,34%. Заключение. Для проведения аналитической диагностики при отравлении клопидогрелом ТСХ-скрининг и УФ-спектрофотометрическое определение необходимо проводить с предварительной ТСХ-очисткой. Изолирование клопидо- грела водой, подкисленной этиловым спиртом (метод Стаса–Отто), не происходит. Наибольшую селективность УФ-спектрофотометрического метода определения клопидогрела в биологическом материале по отношению к матричным компонентам обеспечивал метод изолирования водой, подкисленной серной кислотой (метод В.П. Крамаренко). Эффективность изолирования препарата по методу В.П. Крамаренко составляет 64,23±5,44%. (Russian) [ FROM AUTHOR] Copyright of Farmatsiya (Pharmacy) is the property of Russian Physician Public House Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

A green spectrophotometric method for the simultaneous determination of nasal binary mixture used in respiratory diseases: Applying isosbestic point and chemometric approaches as a resolving tool, greenness evaluation.

Nasal drug combination is a very useful therapy for elevating the symptoms of various respiratory diseases as seasonal allergic rhinitis and infectious respiratory illness as pandemic COVID-19. One of best combination is Fluticasone propionate (FLU) and Azelastine (AZE). In this study, different UV spectrophotometric and chemometric methods have been applied for quantitative analysis of FLU and AZE without previous separation in their pure form, laboratory prepared mixture and pharmaceutical dosage form. Absorbance subtraction (AS) and Amplitude modulation (AM) spectrophotometric methods have been applied for the simultaneous determination of the cited drugs. Besides, three well-known chemometric techniques; namely, classical least squares (CLS), partial least square (PLS), and principal component regression (PCR) have been applied for the simultaneous analysis of both drugs by using spectrophotometric data. To be friendly to the environment, the greenness of the proposed methods was taken into consideration and evaluation of the analytical methods' greenness was done using two green analytical chemistry metrics known as, Analytical Greenness Calculator and an eco-scale scoring method. They indicated that the methods were environmentally friendly in relation to numerous approaches like instrument, reagents, and safety of waste. Analyzing laboratory prepared mixtures including different quantities of FLU and AZE, as well as their marketed dose form, was used to assess the selectivity of the applied methods. The validity of the developed methods was investigated by applying the standard addition technique. The resulting data were statistically compared to those obtained by the official or reported HPLC methods for FLU and AZE, which revealed no significant difference in accuracy and precision at p = 0.05.