zldmЗаводская лаборатория. Диагностика материаловIndustrial laboratory. Diagnostics of materials1028-68612588-0187ООО «Издательство «ТЕСТ-ЗЛ»10.26896/1028-6861-2026-92-3-18-26zldm-2756Research ArticleАНАЛИЗ ВЕЩЕСТВАSUBSTANCES ANALYSISОпределение паклитаксела и ритонавира в плазме крови и органах крыс методом высокоэффективной жидкостной хроматографииDetermination of paclitaxel and ritonavir in blood plasma and organs of rats by HPLCБойкоС. А.BoykoS. A.

Светлана Андреевна Бойко

125047, Москва, Миусская пл., д. 9

Svetlana A. Boyko

9, Miusskaya pl., Moscow, 125047

boiko.s.an@muctr.ruАгаповаА. А.AgapovaA. A.

Анастасия Александровна Агапова

125047, Москва, Миусская пл., д. 9

Anastasia A. Agapova

9, Miusskaya pl., Moscow, 125047

КовшоваТ. С.KovshovaT. S.

Татьяна Сергеевна Ковшова

125047, Москва, Миусская пл., д. 9

Tatyana S. Kovshova

9, Miusskaya pl., Moscow, 125047

КотоваЮ. О.KotovaJ. O.

Юлия Олеговна Котова

125047, Москва, Миусская пл., д. 9

Julia O. Kotova

9, Miusskaya pl., Moscow, 125047

ЕсефьеваТ. Ю.EsefyevaT. Yu.

Татьяна Юрьевна Есефьева

125047, Москва, Миусская пл., д. 9

Tatyana Yu. Esefyeva

9, Miusskaya pl., Moscow, 125047

ВалиховМ. П.ValikhovM. P.

Марат Петрович Валихов

119034, Москва, Кропоткинский пер., д. 23

Marat P. Valikhov

23, Kropotkinskiy per., Moscow, 119034

ГельперинаС. Э.GelperinaS. E.

Светлана Эммануиловна Гельперина

125047, Москва, Миусская пл., д. 9

Svetlana E. Gelperina

9, Miusskaya pl., Moscow, 125047

Российский химико-технологический университет имени Д. И. МенделееваРоссияMendeleev University of Chemical TechnologyRussian FederationФедеральный медицинский исследовательский центр психиатрии и наркологии им. В. П. Сербского Минздрава РоссииРоссияV. Serbsky Federal Medical Research Centre of Psychiatry and Narcology of the Ministry of Health of the Russian FederationRussian FederationРоссийский химико-технологический университет имени Д. И. МенделееваRussian Federation2026260320269231826Copyright © Бойко С.А., Агапова А.А., Ковшова Т.С., Котова Ю.О., Есефьева Т.Ю., Валихов М.П., Гельперина С.Э., 20262026Бойко С.А., Агапова А.А., Ковшова Т.С., Котова Ю.О., Есефьева Т.Ю., Валихов М.П., Гельперина С.Э.Boyko S.A., Agapova A.A., Kovshova T.S., Kotova J.O., Esefyeva T.Y., Valikhov M.P., Gelperina S.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.zldm.ru/jour/article/view/2756

Паклитаксел (PTX) — цитотоксический противоопухолевый агент из группы таксанов, низкая биодоступность и тканевое биораспределение которого могут быть изменены в присутствии ингибиторов ферментов печени и транспортных белков, например, ритонавира (RTV) — антиретровирусного агента, применяемого в терапии ВИЧ-инфекции. Разработана и валидирована методика одновременного определения PTX и RTV в плазме крови, гомогенатах печени, мозга и тестикул крыс методом обращенно-фазовой высокоэффективной жидкостной хроматографии (ВЭЖХ) с диодно-матричным детектированием. Пробоподготовка образцов включала жидкость-жидкостную экстракцию с последующим упариванием экстракта и повторным диспергированием в подвижной фазе с дополнительной очисткой. Диапазон определяемых содержаний PTX составляет 100 – 9090 нг/мл в плазме крови и 25 – 9090 нг/г в гомогенатах органов, RTV — 250 – 9090 нг/г во всех объектах анализа. Предел определения (ПО) PTX в плазме — 100 нг/мл, RTV — 250 нг/мл, в органах — 25 и 250 нг/г соответственно. Разработанная методика показала высокую точность (относительная ошибка Δ < 12 %) и прецизионность (относительное стандартное отклонение RSD < 14 %) во всем диапазоне концентраций; степень извлечения PTX и RTV составила >80 % для всех биологических объектов. Предложенная методика может быть использована при изучении фармакокинетики данной комбинации лекарственных веществ в биологических матрицах.

Paclitaxel (PTX) is a cytotoxic antitumor agent from the taxane group, which low bioavailability and tissue biodistribution can be altered in the presence of inhibitors of liver enzymes and transport proteins. One of them is ritonavir (RTV), an antiretroviral agent used in the treatment of HIV infection. This study describes the development and validation of high-performance liquid chromatography with photodiode-array detection (HPLC-PDA) method for the simultaneous quantitative determination of PTX and RTV in rat blood plasma, liver, brain, and testis homogenates. Sample preparation involved liquid-liquid extraction followed by extract evaporation, redispersion in the mobile phase, and additional purification. Analytes were separated using LC-2030C 3D Plus Prominence-i system (Shimadzu) under reversed-phase chromatography conditions with an isocratic elution mode. The separation was performed on Hawach C18 Universal column (250 × 4.6 mm, 5 μm particle size). The mobile phase consisted of water (A) and acetonitrile (B) in a 50:50 ratio. Detection was carried out at the following wavelengths: for PTX 228 nm (retention time: 16 min), for RTV 240 nm (retention time: 19 min). The method demonstrated linearity over the concentration ranges of 100 – 9090 ng/mL PTX for plasma and 25 – 9090 ng/g for tissues, 250 – 9090 ng/g RTV in all matrices. The LOQs were 100 ng/mL PTX and 250 ng/mL RTV in plasma; 25 ng/g PTX and 250 ng/g RTV in tissues. The developed method exhibited high accuracy (relative error Δ < 12%) and precision (relative standard deviation RSD < 14%) across the entire concentration range. The recoveries for both PTX and RTV exceeded 80% in all biological matrices. In this regard, the method can be used to study the pharmacokinetics of this combination of drugs in biological matrices.

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The authors declare that there are no conflicts of interest present.