Застосування тонкошарової хроматографії в аналізі ефавіренцу

Aim. To carry out the integrated study of visualization conditions of efavirenz on TLC-plates with aplication of standard and particular colored reagents, and the chromatographic behavior of efavirenz using standard mobile phases.Results and discussion. It has been shown that such widely used color...

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Published in:Журнал органічної та фармацевтичної хімії
Date:2020
Volume:18
Issue:1(69)
Pages:58-62
ISSN:2518-1548
Author Affiliations:
  • Oksana I. Slabiak — Ivano-Frankivsk National Medical University
  • Iryna M. Ivanchuk — Ivano-Frankivsk National Medical University — ORCID: 0009-0006-4335-8119
  • Lina Yu. Klimenko — National University of Pharmacy — ORCID: 0000-0002-4857-5706
  • Olena Ye. Mykytenko — National University of Pharmacy — ORCID: 0000-0003-3178-3418
  • Olga V. Antonenko — National University of Pharmacy — ORCID: 0000-0002-0369-6520
Main Authors: Slabiak, Oksana I., Ivanchuk, Iryna M., Klimenko, Lina Yu., Mykytenko, Olena Ye., Antonenko, Olga V.
Format: Article
Language:English
Published: National University of Pharmacy 2020
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Online Access:https://ophcj.nuph.edu.ua/article/view/ophcj.20.197511
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Journal Title:Journal of Organic and Pharmaceutical Chemistry
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Journal of Organic and Pharmaceutical Chemistry
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author Slabiak, Oksana I.
Ivanchuk, Iryna M.
Klimenko, Lina Yu.
Mykytenko, Olena Ye.
Antonenko, Olga V.
author_facet Slabiak, Oksana I.
Ivanchuk, Iryna M.
Klimenko, Lina Yu.
Mykytenko, Olena Ye.
Antonenko, Olga V.
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author_orcid_str_mv 0009-0006-4335-8119
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container_title Журнал органічної та фармацевтичної хімії
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description Aim. To carry out the integrated study of visualization conditions of efavirenz on TLC-plates with aplication of standard and particular colored reagents, and the chromatographic behavior of efavirenz using standard mobile phases.Results and discussion. It has been shown that such widely used color reagents as UV-light, Erdmann reagent, Froehde reagent, Liebermann reagent, sulfuric acid, Marquis reagent, Mandelin reagent, acidified iodoplatinate solution, iodine vapor can be used for efavirenz detection on chromatographic plates. Efavirenz gives the positive detection results with reagents used in the TLC-screening of extracts from the biological material for substances of basic, acid and neutral nature. The chromatographic mobility of efavirenz has been studied in 17 solvents systems; the systems are used as standard mobile phases according to the recommendations of the International Association of Forensic Toxicologists for TLC-screening of organic compounds of acid, neutral and basic nature, and as well as in the general TLC-screening of organic substances in the Ukrainian forensic toxicological laboratories.Experimental part. The chromatographic plates Sorbfil® PTLC-IIH-UV and Merck® TLC Silica gel 60G were used as thin layers.Conclusions. The behavior of efavirenz when developing on TLC-plates with two types of a substrate (plastic and glass) and with/without a luminophor with commonly used colored reagents has been studied. The Rf values of efavirenz under chromatographing conditions in the standard solvent systems used for TLC-screening of organic compounds of acid, neutral and basic nature have been set. Received: 17.12.2019Revised: 12.01.2020Accepted: 27.02.2020
doi_str_mv 10.24959/ophcj.20.197511
first_indexed 2025-07-17T13:00:43Z
format Article
fulltext Journal of Organic and Pharmaceutical Chemistry. – 2020. – Vol. 18, Iss. 1 (69) 58 ISSN 2308-8303 (Print) ISSN 2518-1548 (Online) UDC 615.281.1:543.544.5 https://doi.org/10.24959/ophcj.20.197511 O. I. Slabiak1, I. M. Ivanchuk1, L. Yu. Klimenko2, O. Ye. Mykytenko2, O. V. Antonenko2 1 Ivano-Frankivsk National Medical University, Ukraine 2 National University of Pharmacy, Ukraine 53, Pushkinska str., Kharkiv, 61002, Ukraine. E-mail: lina_klimenko@nuph.edu.ua Application of thin layer chromatography in the analysis of efavirenz Aim. To carry out the integrated study of visualization conditions of efavirenz on TLC-plates with aplication of standard and particular colored reagents, and the chromatographic behavior of efavirenz using standard mobile phases. Results and discussion. It has been shown that such widely used color reagents as UV-light, Erdmann rea- gent, Froehde reagent, Liebermann reagent, sulfuric acid, Marquis reagent, Mandelin reagent, acidified iodoplatinate solution, iodine vapor can be used for efavirenz detection on chromatographic plates. Efavirenz gives the positive detection results with reagents used in the TLC-screening of extracts from the biological material for substances of basic, acid and neutral nature. The chromatographic mobility of efavirenz has been studied in 17 solvents systems; the systems are used as standard mobile phases according to the recommendations of the International Association of Forensic Toxicologists for TLC-screening of organic compounds of acid, neutral and basic nature, and as well as in the general TLC-screening of organic substances in the Ukrainian forensic toxicological laboratories. Experimental part. The chromatographic plates Sorbfil® PTLC-IIH-UV and Merck® TLC Silica gel 60G were used as thin layers. Conclusions. The behavior of efavirenz when developing on TLC-plates with two types of a substrate (plastic and glass) and with/without a luminophor with commonly used colored reagents has been studied. The Rf values of efavirenz under chromatographing conditions in the standard solvent systems used for TLC-screening of organic compounds of acid, neutral and basic nature have been set. Key words: efavirenz; thin layer chromatography; color tests О. І. Слабяк1, І. М. Іванчук1, Л. Ю. Клименко2, О. Є. Микитенко2, О. В. Антоненко2 1 Івано-Франківський національний медичний університет, Україна 2 Національний фармацевтичний університет, Україна Застосування тонкошарової хроматографії в аналізі ефавіренцу Мета. Провести комплексне дослідження умов візуалізації ефавіренцу на ТШХ-пластинах із застосу- ванням стандартних і окремих кольорових реагентів, а також хроматографічної поведінки ефавіренцу з вико- ристанням стандартних рухомих фаз. Результати та їх обговорення. Показано, що для виявлення ефавіренцу на хроматографічних пластинах можна використовувати такі широко відомі проявники, як УФ-світло, реактив Ердмана, реактив Фреде, реактив Лібермана, сульфатна кислота, реактив Маркі, реактив Манделіна, підкислений розчин йодоплатинату, пари йоду. Ефавіренц дає позитивні результати виявлення з реактивами, що використовують в ТШХ-скринінгу витягів з біологічного матеріалу на речовини основного, кислого і нейтрального характеру. Хроматографічну рухливість ефавіренцу досліджено в 17 системах розчинників, серед яких рухомі фази, що застосовують як стандартні згід- но з рекомендаціями Міжнародного комітету з систематичного токсикологічного аналізу Міжнародної асоціації судових токсикологів для ТШХ-скринінгу органічних речовин кислого, нейтрального та основного характеру, а та- кож у загальному ТШХ-скринінгу органічних речовин у судово-токсикологічних лабораторіях України. Експериментальна частина. Як тонкі шари використовували пластини Sorbfil ПТСХ-ІІВ-УФ та Merck TLC Silica gel 60G. Висновки. Досліджено поведінку ефавіренцу при проявленні загальноприйнятими хромогенними ре- агентами на пластинах для ТШХ з двома типами підложки (пластик та скло) та з УФ-індикатором і без нього. Встановлено значення Rf ефавіренцу за умов хроматографування в стандартних системах роз- чинників, що використовуються для ТШХ-скринінгу речовин кислого, нейтрального та основного характеру. Ключові слова: ефавіренц; тонкошарова хроматографія; кольорові реакції О. И. Слабяк1, И. М. Иванчук1, Л. Ю. Клименко2, Е. Е. Микитенко2, О. В. Антоненко2 1 Ивано-Франковский национальный медицинский университет, Украина 2 Национальный фармацевтический университет, Украина Применение тонкослойной хроматографии в анализе эфавиренца Цель. Провести комплексное исследование условий визуализации эфавиренца на ТСХ-пластинах с при- менением стандартных и частных цветных реагентов, а также хроматографического поведения эфави- ренца с использованием стандартных подвижных фаз. Результаты и их обсуждение. Показано, что для обнаружения эфавиренца на хроматографических пласти- нах можно использовать такие широко применяемые проявители, как УФ-свет, реактив Эрдманна, реактив Фреде, реактив Либермана, серная кислота, реактив Марки, реактив Манделина, подкисленный раствор йодопла- тината, пары йода. Эфавиренц дает положительные результаты обнаружения с реактивами, используемыми в ходе ТСХ-скрининга извлечений из биологического материала на вещества основного, кислого и нейтрального характера. Хроматографическая подвижность эфавиренца исследована в 17 системах растворителей, среди которых подвижные фазы, применяемые в качестве стандартных согласно рекомендациям Международного комитета по систематическому токсикологическому анализу Международной ассоциации судебных токси- кологов для ТСХ-скрининга органических веществ кислого, нейтрального и основного характера, а также в общем ТСХ-скрининге органических веществ в судебно-токсикологических лабораториях Украины. Журнал органічної та фармацевтичної хімії. – 2020. – Т. 18, вип. 1 (69) 59 ISSN 2518-1548 (Online) ISSN 2308-8303 (Print) Экспериментальная часть. В качестве тонких слоев использовали пластины Sorbfil ПТСХ-ІІВ-УФ и Merck TLC Silica gel 60G. Выводы. Исследовано поведение эфавиренца при проявлении общепринятыми хромогенными ре- агентами на пластинах для ТСХ с двумя типами подложки (пластик и стекло) и с УФ-индикатором и без него. Установлены значения Rf эфавиренца в условиях хроматографирования в стандартных системах растворителей, используемых для ТСХ-скрининга веществ кислого, нейтрального и основного характера. Ключевые слова: эфавиренц; тонкослойная хроматография; цветные реакции HIV infection is usually treated with drug com- binations consisting of at least three different anti- retroviral medicines. Essential components of this highly active antiretroviral therapy are non-nucleoside and nucleoside reverse transcriptase inhibitors [1, 2]. The group of non-nucleoside reverse transcriptase inhibitors are currently presented by five medicines (nevirapine, delavirdine, efavirenz, etravirine and ril- pivirine) approved by the Food and Drug Administra- tion; four of them (nevirapine, efavirenz, etravirine and rilpivirine) have been approved by the European Union [3 – 5]. Efavirenz is recommended currently as a prefer- red first-line medicine with a low pill burden, once daily dosing, a long half-life allowing for relatively stable plasma concentrations and some forgiveness for doses not taken exactly on the schedule [6, 7]. Efavirenz therapy accompanies with quite a num- ber of side effects showed by psychiatric symptoms, including insomnia, nightmares, memory loss, depres- sion, and anxiety. Efavirenz is characterized by defi- nite neuropsychological symptoms in 50 % of cases; its neurotoxicity exceeds other antiretroviral medi- cines [8 – 10]. The studies of efavirenz showed that in 20 – 50 % of cases the toxic concentrations of the me- dicine in the blood were fixed [11 – 12]. There are cases of acute poisoning due to administration of efavirenz, including cases of suicide attempts [13]. Therefore, in our opinion, efavirenz may be approved as a po- tential toxic compound in forensic toxicology. The method of thin layer chromatography (TLC) is widely used in the process of forensic toxicological examinations for screening and confirming investi- gations – with the purpose of analyte detection and identification, respectively [14, 15]. The main focus is the chromatographic behavior of the substances using standard mobile phases (or solvents systems), as well as the conditions of analyte spots visualiza- tion using standard colored reagents [14, 15]. The aim of our work was the integrated study of visualization conditions of efavirenz on TLC-plates using standard and particular colored reagents, as well as the chromatographic behavior of the substances using standard mobile phases. To fix the results of visualization of the substances to be analyzed 4 developing modes of TLC-plates with two types of a substrate (plastic and glass) and with/ without a luminophor (or UV-indicator) were chosen: 1) immediately after processing the substances with a reagent and after drying the plates at the am- bient temperature; 2) in UV-light at two wavelengths – 254 nm and 365 nm; 3) after heating the plates for 15 min at 110 °C (the plates are covered with glass); 4) in UV-light at two wavelengths – 254 nm and 365 nm – after heating. A number of the reagents studied (hydrogen per- oxide solution, Nessler reagent, perchloric acid, FPN reagent, hydrochloric acid vapor, 1 % H8[Si(W2O7)6] solution, 1 % H7[P(Mo2O7)6] solution, 1 % H7[P(W2O7)6] solution, 1 % H8[Si(Mo2O7)6] solution, formaldehyde/ sulfuric acid, Forrest reagent, Dragendorff reagent, 5 % ferric chloride solution, iodoplatinate solution) do not color efavirenz either before or after heating the plates, and also quench the initial fluorescence both at 254 nm and at 365 nm. The total results of efavirenz visualization on chro- matographic plates are presented in Table 1. Such commonly applied developers as UV-light, Erdmann reagent, Froehde reagent, Liebermann rea- gent, sulfuric acid, Marquis reagent, Mandelin reagent, acidified iodoplatinate solution, iodine vapor can be used for the detection of efavirenz on chromatogra- phic plates. The positive results were recorded when develo- ping efavirenz with the reagents used in the analysis of barbituric acid derivatives [14] – the mercuric chlo- ride/diphenylcarbazone reagent and cobalt nitrate/ ammonia vapor; the spots of various tints of violet color appeared, and they disappeared when heating the plates; in UV-light the spots were not visualized. The most of reagents used for detection and identi- fication of substances of basic nature, including the so- called “generally alkaloid reagents”, allows to visua- lize efavirenz on the TLC-plates. It is colored with the concentrated sulfuric acid, Marquis reagent and the mixture of formaldehyde and the concentrated sulfuric acid, Erdmann reagent, Froehde reagent, Liebermann reagent, Mandelin reagent, acidified iodo- platinate solution. We also processed efavirenz according to the scheme of TLC-screening of the substances of basic nature. Developing the plates with acidified potassium per- manganate solution leads to the formation of brown spots; and after heating the plates the spots are brown. Application of ninhydrin solution in traditional modi- fication for TLC-screening (acidified ninhydrin spray) results in brown spots. Overspraying the plates with FPN reagent and Dragendorff reagent followed by aci- dified iodoplatinate solution does not change the pre- vious results. Journal of Organic and Pharmaceutical Chemistry. – 2020. – Vol. 18, Iss. 1 (69) 60 ISSN 2308-8303 (Print) ISSN 2518-1548 (Online) Table 1 The results of efavirenz visualization on chromatographic plates No. Reagent Stationary phase* Spot color/sensitivity, mg in the sample 1 UV-light (λ = 254 nm) А violet/0.1 В – 2 UV-light (λ = 365 nm) А, В – 3 formaldehyde vapor (for 5 min in the covered cell) A violet (λ = 254 nm)/0.5 yellow (λ = 365 nm)/0.5 B – 4 phosphoric acid [14, p. 2464] pour on A light blue (λ = 365 nm)/0.5 B – 5 Erdmann reagent [14, p. 485] pour on A bright yellow/0.1 B – 6 Froehde reagent [14, p. 478] pour on A pink-brown/0.1 B – 7 Liebermann reagent [14, p. 480] pour on A, B bright yellow/0.1 8 glacial acetic acid [14, p. 2463] pour on A, B yellow/0.5 9 mercuric chloride – diphenylcarbazone reagent [14, p. 2463] spray A, B violet/0.5 10 cobalt nitrate spray, dry + ammonia vapor for 5 min in the covered cell A, B light violet/0.5 11 sulfuric acid [14, p. 488] pour on A, B light yellow (15 min at 110 °C)/0.5 12 Marquis reagent [14, p. 480] pour on A light yellow/0.5 light yellow (15 min at 110 °C) / 0.5 13 Iodine vapor for 5 min in the covered cell A, B brown/0.1 14 Mandelin reagent [14, p. 480] pour on A light brown/0.1 light brown (15 min at 110 °C)/0.1 B pink brown/0.1 pink brown (15 min at 110 °C) / 0.1 15 formaldehyde vapor for 5 min in the covered cell + Mandelin reagent pour on [14, p. 612] A light brown/0.1 light brown (15 min at 110 °C)/0.1 B pink brown/0.1 pink brown (15 min at 110 °C)/0.1 16 acidified potassium permanganate solution [14, p. 478] spray A, B brown/0.1 17 acidified ninhydrin spray [14, p. 2464] spray A, B light brown (15 min at 110 °C)/0.5 18 + FPN reagent [14, p. 478] overspray A, B light brown/0.1 light brown (15 min at 110 °C)/0.1 19 + Dragendorff reagent [14, p. 476] overspray A, B light brown/0.1 light brown (15 min at 110 °C)/0.1 20 + acidified iodoplatinate solution [14, p. 2463] overspray A, B light brown/0.1 light brown (15 min at 110 °C)/0.1 21 Van Urk reagent (acidified p-dimethylaminobenzaldehyde solution in ethanol) [14, p. 476] spray A bright yellow (15 min at 110 °C)/0.1 B yellow (15 min at 110 °C)/0.1 22 + 5 % ferric chloride solution [14, p. 478] overspray A bright yellow (15 min at 110 °C)/0.1 B yellow (15 min at 110 °C)/0.1 23 acidified iodoplatinate solution [14, p. 2463] spray A, B dark brown (15 min at 110 °C)/0.1 Notes: * – А – Sorbfil® PTLC-IIH-UV; В – Merck® TLC Silica gel 60G Журнал органічної та фармацевтичної хімії. – 2020. – Т. 18, вип. 1 (69) 61 ISSN 2518-1548 (Online) ISSN 2308-8303 (Print) Processing the plates directly with iodoplatinate solution does not lead to visible results. Acidified iodo- platinate solution after heating causes the formation of dark brown spots. Developing efavirenz according to the scheme of TLC-screening of the substances of acid and neutral nature leads to the positive results (yellow spots after heating) with Van Urk reagent. Overspraying the plates with 5 % ferric chloride solution does not change the pre- vious results. The chromatographic mobility of efavirenz was studied in 17 solvents systems (Table 2); the systems 1 – 9 were used as standard mobile phases according to the recommendations of the International Asso- ciation of Forensic Toxicologists (TIAFT) for TLC-scre- ening of organic compounds of acid, neutral and basic nature [14]; systems 10 – 12 were used in the general TLC-screening of organic substances in the Ukrainian forensic toxicological laboratories; systems 13 – 17 were studied with the purpose of choosing the optimal in- dividual solvents systems for research of efavirenz. When using the mobile phases 3A, 7A, 8A, 9A the studies were carried out on the plates processed previously with 0.1 mole/L KOH solution in methanol and then dried at 110°С for 30 min. For the mobile phase 6 application the plates were previously pro- cessed with 0.1 mole/L NaBr solution. The results are presented in Table 2. Experimental part Efavirenz was of pharmacopoeial purity. Chloro- form (≥99 %, anhydrous, contains 0.5 – 1.0 % of etha- nol as a stabilizer), ethyl acetate (99.8 %, anhydrous), methanol (≥99.8 %, puriss. p.a., ACS reagent), ammo- nium hydroxide solution (≥25 % NH3 in H2O, puriss. p.a. plus) were purchased from Sigma-Aldrich Co. LLC (USA). All other reagents were of analytical grade. The reference solution 1 (1000 μg/mL) was pre- pared by dissolving 50.0 mg of efavirenz in methanol; the solution was diluted to 50.0 mL with the same solvent. The reference solution 2 (100 μg/mL) was prepared by diluting 5.00 mL of the reference solu- tions 1 to 50.0 mL with methanol. The color reagents were prepared according to [14]. The chromatographic plates Sorbfil® PTLC-IIH-UV (silica gel STC-1HP, PETP, luminophor, silica sol, the frac- tion of 8÷12 μm, the layer thickness of 100 μm) were purchased from IMID LLC (Russia). The chromatogra- phic plates Merck® TLC SILICA GEL 60 (silica gel 60, glass, gypsum, the fraction of 9.5÷11.5 μm, the layer thickness of 140÷160 μm) were purchased from Merck Group (Germany). The part of plates was previously processed with 0.1 mole/L potassium hydroxide solution in metha- nol and then dried at 110°С for 30 min. The part of plates was previously processed with 0.1 mole/L so- dium bromide solution [14]. To choose the developing color reagents in 10 mL of the reference solution 1 were applied on the pla- tes of both types, and then the reagents were sprayed or poured onto the plates. The results were fixed vi- sually at once and after drying the plate, then the pla- tes were developed in UV-light with the wavelength of 254 nm and 365 nm. At the next stage the plates were heated for 15 min at 110 °C (the plates were co- vered with a glass plate), and after that colors of spots were fixed in visible and UV-light one more time. To determine sensitivity of the developing color rea- gents the same experiments were carried out using 1 and 10 mL of the reference solutions 2 of the substances. Table 2 The Rf values for efavirenz Mobile phase Rf of efavirenz (n = 3) Sorbfil® PTLC-PH- UV Merck® TLC Silica gel 60G 1 chloroform – acetone (8:2) 0.65 0.67 2 ethyl acetate 0.85 0.89 3 chloroform – methanol (9:1) 0.76 0.71 3А* chloroform – methanol (9:1) 0.70 0.72 4 ethyl acetate – methanol – 25 % NH3 (85:10:5) 0.18 0.11 5 methanol 0.87 0.82 6 methanol – n-butanol (6:4)** 0.90 0.87 7 methanol – 25 % NH3 (100:1,5) 0.84 0.89 7А* methanol – 25 % NH3 (100:1,5) 0.76 0.74 8 cyclohexane – toluene – diethylamine (75:15:10) 0.05 0.07 8А* cyclohexane – toluene – diethylamine (75:15:10) 0.00 0.00 9 acetone 0.84 0.85 9А* acetone 0.90 0.92 10 chloroform – dioxane – acetone – 25 % NH3 (47,5:45:5:2,5) 0.35 0.39 11 toluene – acetone – ethanol – 25 % NH3 (45:45:7,5:2,5) 0.82 0.85 12 chloroform – n-butanol – 25 % NH3 (70:40:5) 0.90 0.93 13 chloroform 0.00 0.00 14 chloroform – methanol (1:1) 0.85 0.89 15 toluene – CH3COOH conc. (3:1) 0.10 0.15 16 chloroform – methanol – CH3COOH conc. (90:10:1) 0.25 0.29 17 toluene – methanol – CH3COOH conc. (9:1:1) 0.85 0.83 Notes: * – 0.1 M KOH in CH3OH, 110°С, 30 min; ** – 0.1 M NaBr Journal of Organic and Pharmaceutical Chemistry. – 2020. – Vol. 18, Iss. 1 (69) 62 ISSN 2308-8303 (Print) ISSN 2518-1548 (Online) Chromatographing was carried out in cells with the volume of 500 mL; 50 mL of the corresponding TLC-systems were placed into them. The cell was saturated for 30 min. In 10 mL of the reference so- lutions 1 of the substance to be researched were applied on the start line in the distance of 1 cm from the plate edge. The solvent path length was 8 cm. After reaching the finish line by the mobile phase the plate was taken out from the cell, dried at the am- bient temperature and developed with the correspon- ding reagents. Conclusions The behavior of efavirenz when developing with commonly used colored reagents on TLC plates with two types of a substrate (plastic and glass) and with/ without a luminophor (or UV-indicator) has been stu- died. The results of efavirenz development with rea- gents used for TLC-screening of organic compounds of acid, neutral and basic nature are presented. The Rf va- lues for efavirenz have been determined using diffe- rent types of TLC-plates for solvent systems used as standard mobile phases according to the recommen- dations of the International Association of Forensic Toxicologists for TLC-screening of organic compounds of acid, neutral and basic nature, and also in the ge neral TLC-screening of organic substances in the Ukrainian forensic toxicological laboratories. Conflict of interests: authors have no conflict of interests to declare. References 1. Usach, I.; Melis, V.; Peris, J.-E. Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability. Journal of the International AIDS Society 2013, 16 (1), 18567. https://doi.org/10.7448/ias.16.1.18567. 2. Waters, L.; John, L.; Nelson, M. Non-nucleoside reverse transcriptase inhibitors: a review. International Journal of Clinical Practice 2007, 61 (1), 105–118. https://doi.org/10.1111/j.1742-1241.2006.01146.x. 3. De Clercq, E. The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection. Antiviral Research 1998, 38 (3), 153–179. https://doi.org/10.1016/S0166-3542(98)00025-4. 4. Rakhmanina, N. Y.; van den Anker, J. N. Efavirenz in the therapy of HIV infection. Expert Opinion on Drug Metabolism & Toxicology 2010, 6 (1), 95–103. https://doi.org/10.1517/17425250903483207. 5. Bastos, M. M.; Costa, C. C. P.; Bezerra, T. C.; da Silva, F. d. C.; Boechat, N. Efavirenz a nonnucleoside reverse transcriptase inhibitor of first-generation: Approaches based on its medicinal chemistry. Eur. J. Med. Chem. 2016, 108, 455–465. https://doi.org/10.1016/j.ejmech.2015.11.025. 6. Best, B. M.; Goicoechea, M. Efavirenz – Still First-line King? Expert Opinion on Drug Metabolism & Toxicology 2008, 4 (7), 965–972. https://doi. org/10.1517/17425255.4.7.965. 7. Andany, N.; Gold, W. L. Single-tablet antiretroviral treatment (once daily). Canadian Medical Association Journal 2016, 188 (13), 971. https://doi. org/10.1503/cmaj.151412. 8. Kenedi, C. A.; Goforth, H. W. A Systematic Review of the Psychiatric Side-Effects of Efavirenz. AIDS and Behavior 2011, 15 (8), 1803–1818. https:// doi.org/10.1007/s10461-011-9939-5. 9. Decloedt, E. H.; Maartens, G. Neuronal toxicity of efavirenz: a systematic review. Expert Opinion on Drug Safety 2013, 12 (6), 841–846. https:// doi.org/10.1517/14740338.2013.823396. 10. Abers, M. S.; Shandera, W. X.; Kass, J. S. Neurological and Psychiatric Adverse Effects of Antiretroviral Drugs. CNS Drugs 2014, 28 (2), 131–145. https://doi.org/10.1007/s40263-013-0132-4. 11. Mutwa, P. R.; Fillekes, Q.; Malgaz, M.; Tuyishimire, D.; Kraats, R. v. d.; Boer, K. R.; Burger, D. M.; van Schaik, R. H. N.; Muganga, N.; Geelen, S. P. M. Mid-Dosing Interval Efavirenz Plasma Concentrations in HIV-1–Infected Children in Rwanda: Treatment Efficacy, Tolerability, Adherence, and the In- fluence of CYP2B6 Polymorphisms. JAIDS Journal of Acquired Immune Deficiency Syndromes 2012, 60 (4), 400–404. https://doi.org/10.1097/ QAI.0b013e3182569f57. 12. Fillekes, Q.; Natukunda, E.; Balungi, J.; Kendall, L.; Bwakura-Dangarembizi, M.; Keishanyu, R.; Ferrier, A.; Lutakome, J.; Gibb, D. M.; Burger, D. M.; Walker, A. S. Pediatric Underdosing of Efavirenz: A Pharmacokinetic Study in Uganda. JAIDS Journal of Acquired Immune Deficiency Syndromes 2011, 58 (4), 392–398. https://doi.org/10.1097/QAI.0b013e318235e560. 13. Mollan, K. R.; Smurzynski, M.; Eron, J. J.; Daar, E. S.; Campbell, T. B.; Sax, P. E.; Gulick, R. M.; Na, L.; O’Keefe, L.; Robertson, K. R.; Tierney, C. Associa- tion Between Efavirenz as Initial Therapy for HIV-1 Infection and Increased Risk for Suicidal Ideation or Attempted or Completed Suicide: An Analysis of Trial Data. Annals of Internal Medicine 2014, 161 (1), 1–10. https://doi.org/10.7326/m14-0293. 14. Moffat A.C.; Osselton M.D.; Widdop B. Clarke’s analysis of drugs and poisons in pharmaceuticals, body fluids and postmortem material. 4 ed.; Phar- maceutical Press: London, 2011. 15. Jickells, S.; Negrusz, A., Clarke’s Analytical Forensic Toxicology. Pharmaceutical Press: London, 2008. Received: 17. 12. 2019 Revised: 12. 01. 2020 Accepted: 27. 02. 2020 The research was carried out according to the budget themes of the Ministry of Public Health of Ukraine “Study of organizational, marketing, pharmacoeconomic, technological, pharmacological and qualitative aspects of medicines of natural and synthetic origin” (the state registration No. 0113U004136; research period 2013 – 2020) and “Chemical and toxicological analysis of biologically active substances and medicines” (the state registration No. 011411000958; the research period 2014 – 2020).
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spelling oai:ojs.journals.uran.ua:article-1975112026-08-24T18:04:29Z Application of thin layer chromatography in the analysis of efavirenz Применение тонкослойной хроматографии в анализе эфавиренца Застосування тонкошарової хроматографії в аналізі ефавіренцу Slabiak, Oksana I. Ivanchuk, Iryna M. Klimenko, Lina Yu. Mykytenko, Olena Ye. Antonenko, Olga V. эфавиренц тонкослойная хроматография цветные реакции УДК 615.281.1 543.544.5 ефавіренц тонкошарова хроматографія кольорові реакції УДК 615.281.1 543.544.5 efavirenz thin layer chromatography color tests UDC 615.281.1 543.544.5 Aim. To carry out the integrated study of visualization conditions of efavirenz on TLC-plates with aplication of standard and particular colored reagents, and the chromatographic behavior of efavirenz using standard mobile phases.Results and discussion. It has been shown that such widely used color reagents as UV-light, Erdmann reagent, Froehde reagent, Liebermann reagent, sulfuric acid, Marquis reagent, Mandelin reagent, acidified iodoplatinate solution, iodine vapor can be used for efavirenz detection on chromatographic plates. Efavirenz gives the positive detection results with reagents used in the TLC-screening of extracts from the biological material for substances of basic, acid and neutral nature. The chromatographic mobility of efavirenz has been studied in 17 solvents systems; the systems are used as standard mobile phases according to the recommendations of the International Association of Forensic Toxicologists for TLC-screening of organic compounds of acid, neutral and basic nature, and as well as in the general TLC-screening of organic substances in the Ukrainian forensic toxicological laboratories.Experimental part. The chromatographic plates Sorbfil® PTLC-IIH-UV and Merck® TLC Silica gel 60G were used as thin layers.Conclusions. The behavior of efavirenz when developing on TLC-plates with two types of a substrate (plastic and glass) and with/without a luminophor with commonly used colored reagents has been studied. The Rf values of efavirenz under chromatographing conditions in the standard solvent systems used for TLC-screening of organic compounds of acid, neutral and basic nature have been set. Received: 17.12.2019Revised: 12.01.2020Accepted: 27.02.2020 Цель. Провести комплексное исследование условий визуализации эфавиренца на ТСХ-пластинах с применением стандартных и частных цветных реагентов, а также хроматографического поведения эфавиренца с использованием стандартных подвижных фаз.Результаты и их обсуждение. Показано, что для обнаружения эфавиренца на хроматографических пластинах можно использовать такие широко применяемые проявители, как УФ-свет, реактив Эрдманна, реактив Фреде, реактив Либермана, серная кислота, реактив Марки, реактив Манделина, подкисленный раствор йодоплатината, пары йода. Эфавиренц дает положительные результаты обнаружения с реактивами, используемыми в ходе ТСХ-скрининга извлечений из биологического материала на вещества основного, кислого и нейтрального характера. Хроматографическая подвижность эфавиренца исследована в 17 системах растворителей, среди которых подвижные фазы, применяемые в качестве стандартных согласно рекомендациям Международного комитета по систематическому токсикологическому анализу Международной ассоциации судебных токсикологов для ТСХ-скрининга органических веществ кислого, нейтрального и основного характера, а также в общем ТСХ-скрининге органических веществ в судебно-токсикологических лабораториях Украины.Экспериментальная часть. В качестве тонких слоев использовали пластины Sorbfil ПТСХ-ІІВ-УФ и Merck TLC Silica gel 60G.Выводы. Исследовано поведение эфавиренца при проявлении общепринятыми хромогенными реагентами на пластинах для ТСХ с двумя типами подложки (пластик и стекло) и с УФ-индикатором и без него. Установлены значения Rf эфавиренца в условиях хроматографирования в стандартных системах растворителей, используемых для ТСХ-скрининга веществ кислого, нейтрального и основного характера. Received: 17.12.2019Revised: 12.01.2020Accepted: 27.02.2020 Мета. Провести комплексне дослідження умов візуалізації ефавіренцу на ТШХ-пластинах із застосуванням стандартних і окремих кольорових реагентів, а також хроматографічної поведінки ефавіренцу з використанням стандартних рухомих фаз.Результати та їх обговорення. Показано, що для виявлення ефавіренцу на хроматографічних пластинах можна використовувати такі широко відомі проявники, як УФ-світло, реактив Ердмана, реактив Фреде, реактив Лібермана, сульфатна кислота, реактив Маркі, реактив Манделіна, підкислений розчин йодоплатинату, пари йоду. Ефавіренц дає позитивні результати виявлення з реактивами, що використовують в ТШХ-скринінгу витягів з біологічного матеріалу на речовини основного, кислого і нейтрального характеру. Хроматографічну рухливість ефавіренцу досліджено в 17 системах розчинників, серед яких рухомі фази, що застосовують як стандартні згідно з рекомендаціями Міжнародного комітету з систематичного токсикологічного аналізу Міжнародної асоціації судових токсикологів для ТШХ-скринінгу органічних речовин кислого, нейтрального та основного характеру, а також у загальному ТШХ-скринінгу органічних речовин у судово-токсикологічних лабораторіях України.Експериментальна частина. Як тонкі шари використовували пластини Sorbfil ПТСХ-ІІВ-УФ та Merck TLC Silica gel 60G.Висновки. Досліджено поведінку ефавіренцу при проявленні загальноприйнятими хромогенними реагентами на пластинах для ТШХ з двома типами підложки (пластик та скло) та з УФ-індикатором і без нього. Встановлено значення Rf ефавіренцу за умов хроматографування в стандартних системах розчинників, що використовуються для ТШХ-скринінгу речовин кислого, нейтрального та основного характеру. Received: 17.12.2019Revised: 12.01.2020Accepted: 27.02.2020 National University of Pharmacy 2020-03-05 Article Article application/pdf https://ophcj.nuph.edu.ua/article/view/ophcj.20.197511 10.24959/ophcj.20.197511 Journal of Organic and Pharmaceutical Chemistry; Vol. 18 No. 1(69) (2020); 58-62 Журнал органической и фармацевтической химии; Том 18 № 1(69) (2020); 58-62 Журнал органічної та фармацевтичної хімії; Том 18 № 1(69) (2020); 58-62 2518-1548 2308-8303 en https://ophcj.nuph.edu.ua/article/view/ophcj.20.197511/198323 Copyright (c) 2020 Oksana I. Slabiak, Iryna M. Ivanchuk, Lina Yu. Klimenko, Olena Ye. Mykytenko, Olga V. Antonenko https://creativecommons.org/licenses/by/4.0
spellingShingle ефавіренц
тонкошарова хроматографія
кольорові реакції
УДК 615.281.1
543.544.5
Slabiak, Oksana I.
Ivanchuk, Iryna M.
Klimenko, Lina Yu.
Mykytenko, Olena Ye.
Antonenko, Olga V.
Застосування тонкошарової хроматографії в аналізі ефавіренцу
title Застосування тонкошарової хроматографії в аналізі ефавіренцу
title_alt Application of thin layer chromatography in the analysis of efavirenz
Применение тонкослойной хроматографии в анализе эфавиренца
title_full Застосування тонкошарової хроматографії в аналізі ефавіренцу
title_fullStr Застосування тонкошарової хроматографії в аналізі ефавіренцу
title_full_unstemmed Застосування тонкошарової хроматографії в аналізі ефавіренцу
title_short Застосування тонкошарової хроматографії в аналізі ефавіренцу
title_sort застосування тонкошарової хроматографії в аналізі ефавіренцу
topic ефавіренц
тонкошарова хроматографія
кольорові реакції
УДК 615.281.1
543.544.5
topic_facet эфавиренц
тонкослойная хроматография
цветные реакции
УДК 615.281.1
543.544.5
ефавіренц
тонкошарова хроматографія
кольорові реакції
УДК 615.281.1
543.544.5
efavirenz
thin layer chromatography
color tests
UDC 615.281.1
543.544.5
url https://ophcj.nuph.edu.ua/article/view/ophcj.20.197511
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