Influence of traditional Chinese medicines on the <i>in vivo</i> metabolism of lopinavir/ritonavir based on UHPLC-MS/MS analysis

Linlin Li; Xinxiang Yu; Dongmin Xie; Ningning Peng; Weilin Wang; Decai Wang; Binglong Li

doi:10.1016/j.jpha.2021.06.006

Volume 12 Issue 2

May 2022

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Linlin Li, Xinxiang Yu, Dongmin Xie, Ningning Peng, Weilin Wang, Decai Wang, Binglong Li. Influence of traditional Chinese medicines on the in vivo metabolism of lopinavir/ritonavir based on UHPLC-MS/MS analysis[J]. Journal of Pharmaceutical Analysis, 2022, 12(2): 270-277. doi: 10.1016/j.jpha.2021.06.006

Citation:

Linlin Li, Xinxiang Yu, Dongmin Xie, Ningning Peng, Weilin Wang, Decai Wang, Binglong Li. Influence of traditional Chinese medicines on the in vivo metabolism of lopinavir/ritonavir based on UHPLC-MS/MS analysis[J]. Journal of Pharmaceutical Analysis, 2022, 12(2): 270-277. doi: 10.1016/j.jpha.2021.06.006

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Influence of traditional Chinese medicines on the in vivo metabolism of lopinavir/ritonavir based on UHPLC-MS/MS analysis

doi: 10.1016/j.jpha.2021.06.006

Department of Clinical Pharmacy, School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, Shandong, 271016, China

Funds:

This work was supported by the Development Plan of Science and Technology of Traditional Chinese Medicine in Shandong Province (Grant No.: 2019–0350) and the Development Plan of Medical and Health Technology in Shandong Province (Grant No.: 2018WS133).

Received Date: Jan. 19, 2021
Accepted Date: Jun. 24, 2021
Rev Recd Date: Jun. 17, 2021
Publish Date: Jun. 25, 2021

Abstract

Abstract

A fast, reliable, and cost-effective liquid chromatography-tandem mass spectrometry method was established to determine the effects of the traditional Chinese medicine employed to treat coronavirus disease 2019, namely, Lianhua Qingwen granules, Huoxiang Zhengqi capsules, Jinhua Qinggan granules, Shufeng Jiedu capsules, and Angong Niuhuang pills, on the pharmacokinetics of lopinavir/ritonavir in rats. Blood samples were prepared using the protein precipitation method and atazanavir was selected as the internal standard (IS). Separation was performed on an Agilent ZORBAX eclipse plus C₁₈ (2.1 mm×50 mm, 1.8 μm) column using acetonitrile and water containing 0.1% formic acid as the mobile phase for gradient elution. The flow rate was 0.4 mL/min and the injection volume was 2 μL. Agilent Jet Stream electrospray ionization was used for mass spectrometry detection under positive ion multiple reaction monitoring mode at a transition of m/z 629.3→447.3 for lopinavir, m/z 721.3→296.1 for ritonavir, and m/z 705.4→168.1 for the IS. The method showed good linearity in the concentration range of 25–2500 ng/mL (r=0.9981) for lopinavir and 5–500 ng/mL (r=0.9984) for ritonavir. The intra-day and inter-day precision and accuracy were both within ±15%. Items, such as dilution reliability and residual effect, were also within the acceptable limits. The method was used to determine the effects of five types of traditional Chinese medicines on the pharmacokinetics of lopinavir/ritonavir in rats. The pharmacokinetic results showed that the half-life of ritonavir in the groups administered Lianhua Qingwen granules and Huoxiang Zhengqi capsules combined with lopinavir/ritonavir was prolonged by approximately 1.5- to 2-fold relative to that in the control group. Similarly, the pharmacokinetic parameters of lopinavir were altered. Overall, the results of this study offer important theoretical parameters for the effective clinical use of five types of traditional Chinese medicines combined with lopinavir/ritonavir to reduce the occurrence of clinical adverse reactions.

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