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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Main Authors: Lili Cui, Zhipeng Wang, Shi Qiu, Mengwei Zhang, Yanping Liu, Fengjing Xu, Xinhua Song, Shouhong Gao, Wansheng Chen
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Analytical Methods in Chemistry
Online Access:http://dx.doi.org/10.1155/2022/6058445
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author Lili Cui
Zhipeng Wang
Shi Qiu
Mengwei Zhang
Yanping Liu
Fengjing Xu
Xinhua Song
Shouhong Gao
Wansheng Chen
author_facet Lili Cui
Zhipeng Wang
Shi Qiu
Mengwei Zhang
Yanping Liu
Fengjing Xu
Xinhua Song
Shouhong Gao
Wansheng Chen
author_sort Lili Cui
collection DOAJ
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-C8 (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 (R2) 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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publishDate 2022-01-01
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spelling doaj-art-9aebf49b5c1d414baf8908b3343689e02025-02-03T01:25:21ZengWileyJournal of Analytical Methods in Chemistry2090-88732022-01-01202210.1155/2022/6058445LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic StudyLili Cui0Zhipeng Wang1Shi Qiu2Mengwei Zhang3Yanping Liu4Fengjing Xu5Xinhua Song6Shouhong Gao7Wansheng Chen8Department of PharmacyDepartment of PharmacyResearch and Development Center of Chinese Medicine Resources and BiotechnologyChemistry and Biological Engineering CollegeChemistry and Biological Engineering CollegeDepartment of PharmacyDepartment of PharmacyDepartment of PharmacyDepartment of PharmacyHydroxychloroquine (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-C8 (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 (R2) 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.http://dx.doi.org/10.1155/2022/6058445
spellingShingle Lili Cui
Zhipeng Wang
Shi Qiu
Mengwei Zhang
Yanping Liu
Fengjing Xu
Xinhua Song
Shouhong Gao
Wansheng Chen
LC-MS/MS Method for Determination of Hydroxychloroquine and Metabolites: Application in a Pharmacokinetic Study
Journal of Analytical Methods in Chemistry
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
url http://dx.doi.org/10.1155/2022/6058445
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