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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi
2022
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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. |
format | Online Article Text |
id | pubmed-8733715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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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