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Федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный медицинский университет имени Н.Н. Бурденко" Министерства здравоохранения Российской Федерации

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PHARMACEUTICAL ANALYSIS OF LIDOCAINE HYDROCHLORIDE INJECTION SOLUTIONS USING THE SPECTROPHOTOMETRIC METHOD

Tikhonova

Veronika Evgenievna

veronikago009@gmail.comhttps://orcid.org/0000-0001-7387-8410Sukhetskaya

Ekaterina Anatolievna

Suhetzckaya2015@yandex.ruhttps://orcid.org/0000-0002-2636-6938

Voronezh State Medical University named after N. N. Burdenko

20042023

12S2573575

31012023

04032023

2023

Lidocaine ((2-Diethylamino)-N-(2,6-dimethylphenyl)acetamide (in the form of hydrochloride)) a drug of a group of local anesthetics for all types of local anesthesia, as well as an antiarrhythmic agent used in the treatment of acute myocardial infarction, in the postoperative period, with ventricular fibrillation, etc. The drug has a number of side effects, the degree of danger of which for human life and health depends on the concentration of the drug in blood plasma. This necessitates the quantitative analysis of drugs containing lidocaine hydrochloride. The purpose of this study was to evaluate the quantitative content of lidocaine hydrochloride in injection solutions from different manufacturers by spectrophotometric method. Materials and methods. Lidocaine hydrochloride preparations of 20 mg/ml in the form of injection solutions manufactured by Solopharm (Russia, St. Petersburg), Renewal (Russia, Novosibirsk) and JSC "Pharmasynthesis" (Russia, Irkutsk) were selected as the objects of the study. To quantify the content of the active substance, a spectrophotometric method was used, the optical density of the obtained solutions was measured on a Shimadzu UV-1800 spectrophotometer. Results and conclusion. The concentrations of the preparations calculated using the equation of the calibration schedule correspond to those stated on the packaging and instructions from the manufacturer, which allows us to conclude that injection solutions containing lidocaine hydrochloride meet the requirements of regulatory documents.

lidocaine hydrochloridepharmaceutical analysisspectrophotometryoptical densityquantitative determination

лидокаина гидрохлоридфармацевтический анализспектрофотометрияоптическая плотностьколичественное определение

Relevance Lidocaine ((2-Diethylamino)-N-(2,6-dimethylphenyl)acetamide (in the form of hydrochloride)) a medicinal product of a group of local anesthetics, as well as antiarrhythmic agents. It is a white powder, very easily soluble in water, which allows it to be used in the form of aqueous solutions for injection. The main structural elements of the drug are an aromatic ring, an amide bond and a tertiary nitrogen atom [1, 2]. Lidocaine hydrochloride is used for all types of local anesthesia, including conduction, epidural, spinal, intraligmental during surgical interventions and other manipulations in which there is a need for tissue numbness in a certain area. This drug should be used with extreme caution due to possible systemic toxic reactions to a local anesthetic, which directly depends on the concentration of the drug in human blood plasma. Thus, with an increase in the concentration of lidocaine in plasma from 5 to 25 micrograms/ml, symptoms from muscle twitching, lowering blood pressure, visual impairment, dizziness, numbness of the tongue to tonic-clonic seizures, central nervous system depression, respiratory arrest up to the development of coma are consistently observed [3, 4, 5]. All this makes it necessary to conduct a thorough analysis of the concentration of the drug in the dispensed dosage forms of both factory and extemporal manufacture. OBJECTIVE: to evaluate the quantitative content of lidocaine hydrochloride in injection solutions from different manufacturers by spectrophotometric method. MATERIALS AND METHODS The objects of the study were lidocaine hydrochloride preparations in the form of injection solutions at a concentration of 20 mg/ml from different manufacturers: Lidocaine from Solopharm (Russia, St. Petersburg) series 740622, Lidocaine Bufus from Renewal (Russia, Novosibirsk) series 60422, Lidocaine from Pharmasynthesis JSC (Russia, Irkutsk) series 20122. The samples were purchased from pharmacy retail organizations in Voronezh. The studied solutions were transparent colorless liquids packed with 2 ml Blow-Fill-Seal technology. The content of lidocaine hydrochloride in medicinal preparations was calculated according to a calibration schedule. To construct a calibration schedule, a series of solutions of various concentrations were prepared from the substance of the drug: 0.015 mg/ml, 0.025 mg/ml, 0.05 mg/ml, 0.075 mg/ml and 0.1 mg/ml. The optical density of the obtained solutions was measured using a Shimadzu UV-1800 spectrophotometer (Japan) in quartz glass cuvettes with a working layer thickness of 10 mm at a wavelength of 262 nm. The comparison solution was purified water. The quality control of lidocaine hydrochloride substance was carried out using qualitative reactions (with 5% cobalt nitrate solution) and methods of quantitative determination (acid-base titration) of lidocaine hydrochloride according to the requirements of the State Pharmacopoeia of the 14th edition. Spectrophotometric analysis of the objects of study was carried out according to the following method: 5 ml of each sample was introduced into a 100 ml volumetric flask and brought to the mark with purified water (solution A). Further, 2.5 ml of solution A was taken from each flask with a measuring pipette and transferred to flasks with a capacity of 50 ml and also brought to the mark with purified water. The optical density of the obtained solutions was determined on a Shimadzu UV-1800 spectrophotometer in quartz glass cuvettes with a thickness of 10 mm at a wavelength of 262 nm, using purified water as a comparison solution. The concentration of the initial samples was calculated according to the equation of the calibration graph obtained earlier. Results Based on the measurement results, a calibration graph was constructed in the concentration range from 0.015 to 0.1 mg/ml. The Booger-Lambert-Behr law is fulfilled within the selected concentration limits. The equation of the calibration graph for lidocaine hydrochloride has the form y = 1.713x, where y is the optical density of the analyzed solution, and x is the concentration of the analyzed solution, mg/ ml. The average optical density value for Solopharm's lidocaine hydrochloride solution of 20 mg/ml was 0.090, Renewal's 0.089, and Pharmasynthesis JSC's 0.090. The average concentrations of the studied drugs were 21.016 mg/ml, 20.876 mg/ml, 21.062 mg/ml, respectively, taking into account dilution, while the standard deviation (SD) in all tests did not exceed 0.2089, and the standard error of the mean (SEM) was 0.09342. The analysis and statistical processing of the results was carried out using the Microsoft Excel 2010 software package. Statistical data processing was carried out using descriptive statistics methods (n = 5, p = 0.95). Discussion Analysis of the quantitative content of lidocaine hydrochloride in injection solutions using the spectrophotometric method allowed to obtain statistically reliable data on the concentrations of the active substance in medicines from different manufacturers and to conclude about their quality according to the requirements of regulatory documents. Conclusion Thus, the studied solutions of drugs in the form of parenteral dosage forms with lidocaine hydrochloride at a concentration of 20 mg/ml of Solopharm (Russia, St. Petersburg) series 740622, Renewal (Russia, Novosibirsk) series 60422, JSC "Pharmasynthesis" (Russia, Irkutsk) series 20122 meet the requirements of regulatory documents.

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