LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study

Hydroxychloroquine (HCQ) was originally used as an antimalarial and immunomodulation drug. We developed and validated a simple and sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantitation of HCQ and its three metabolites in rat...

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Autores principales: Cui, Lili, Wang, Zhipeng, Qiu, Shi, Zhang, Mengwei, Liu, Yanping, Xu, Fengjing, Song, Xinhua, Gao, Shouhong, Chen, Wansheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733715/
https://www.ncbi.nlm.nih.gov/pubmed/35003822
http://dx.doi.org/10.1155/2022/6058445
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author Cui, Lili
Wang, Zhipeng
Qiu, Shi
Zhang, Mengwei
Liu, Yanping
Xu, Fengjing
Song, Xinhua
Gao, Shouhong
Chen, Wansheng
author_facet Cui, Lili
Wang, Zhipeng
Qiu, Shi
Zhang, Mengwei
Liu, Yanping
Xu, Fengjing
Song, Xinhua
Gao, Shouhong
Chen, Wansheng
author_sort Cui, Lili
collection PubMed
description Hydroxychloroquine (HCQ) was originally used as an antimalarial and immunomodulation drug. We developed and validated a simple and sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantitation of HCQ and its three metabolites in rat blood, and reported their pharmacokinetic parameters. The chromatographic separation and detection of analytes were achieved within 4 min on ZORBAX SB-C(8) (3.5 μm, 2.1 × 150 mm) column with gradient elution, and the flow rate was 0.25 mL/min. Simple protein precipitation was successfully applied for sample pretreatment. The HCQ displays a good linearity in the range of 2.0–5000.0 ng/mL, and the three metabolites also show good linearity ranging from 1.0 to 2500.0 ng/mL, with all correlation coefficients (R(2)) better than 0.98. In conclusion, this rapid, sensitive method was successfully developed, validated, and then applied to a pharmacokinetic study of HCQ in rat model in high dose. The results of the pharmacokinetic study presented an average half-life time 21.14 ± 10.31 h (mean ± SD) of HCQ, which is much shorter in human compared to that in mice. For the three metabolites, longer half-life times (approximately 100 h) were shown in rat.
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spelling pubmed-87337152022-01-07 LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study Cui, Lili Wang, Zhipeng Qiu, Shi Zhang, Mengwei Liu, Yanping Xu, Fengjing Song, Xinhua Gao, Shouhong Chen, Wansheng J Anal Methods Chem Research Article Hydroxychloroquine (HCQ) was originally used as an antimalarial and immunomodulation drug. We developed and validated a simple and sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantitation of HCQ and its three metabolites in rat blood, and reported their pharmacokinetic parameters. The chromatographic separation and detection of analytes were achieved within 4 min on ZORBAX SB-C(8) (3.5 μm, 2.1 × 150 mm) column with gradient elution, and the flow rate was 0.25 mL/min. Simple protein precipitation was successfully applied for sample pretreatment. The HCQ displays a good linearity in the range of 2.0–5000.0 ng/mL, and the three metabolites also show good linearity ranging from 1.0 to 2500.0 ng/mL, with all correlation coefficients (R(2)) better than 0.98. In conclusion, this rapid, sensitive method was successfully developed, validated, and then applied to a pharmacokinetic study of HCQ in rat model in high dose. The results of the pharmacokinetic study presented an average half-life time 21.14 ± 10.31 h (mean ± SD) of HCQ, which is much shorter in human compared to that in mice. For the three metabolites, longer half-life times (approximately 100 h) were shown in rat. Hindawi 2022-01-05 /pmc/articles/PMC8733715/ /pubmed/35003822 http://dx.doi.org/10.1155/2022/6058445 Text en Copyright © 2022 Lili Cui et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cui, Lili
Wang, Zhipeng
Qiu, Shi
Zhang, Mengwei
Liu, Yanping
Xu, Fengjing
Song, Xinhua
Gao, Shouhong
Chen, Wansheng
LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study
title LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study
title_full LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study
title_fullStr LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study
title_full_unstemmed LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study
title_short LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study
title_sort lc-ms/ms method for determination of hydroxychloroquine and metabolites: application in a pharmacokinetic study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733715/
https://www.ncbi.nlm.nih.gov/pubmed/35003822
http://dx.doi.org/10.1155/2022/6058445
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