Simultaneous Quantification of Propylthiouracil and Its <i>N</i>-β-<span style="font-variant: small-caps">d</span> Glucuronide by HPLC-MS/MS: Application to a Metabolic Study

Propylthiouracil (PTU) is commonly prescribed for the management of hyperthyroidism and thyrotoxicosis. Although the exact mechanism of action is not fully understood, PTU is associated with hepatoxicity in pediatric population. Glucuronidation mediated by uridine 5′-diphospho-glucuronosyltransferas...

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Autores principales:	Min Li, Qingfeng He, Li Yao, Xiaofeng Wang, Zhijia Tang, Xiao Zhu, Hai-Shu Lin, Xiaoqiang Xiang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	propylthiouracil propylthiouracil glucuronide in vitro human liver microsomes UGT1A9 HPLC-MS/MS Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/a8d10f0df6d343ab9a5a1a043188ee4c
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spelling	oai:doaj.org-article:a8d10f0df6d343ab9a5a1a043188ee4c2021-11-25T18:40:06ZSimultaneous Quantification of Propylthiouracil and Its <i>N</i>-β-<span style="font-variant: small-caps">d</span> Glucuronide by HPLC-MS/MS: Application to a Metabolic Study10.3390/ph141111941424-8247https://doaj.org/article/a8d10f0df6d343ab9a5a1a043188ee4c2021-11-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1194https://doaj.org/toc/1424-8247Propylthiouracil (PTU) is commonly prescribed for the management of hyperthyroidism and thyrotoxicosis. Although the exact mechanism of action is not fully understood, PTU is associated with hepatoxicity in pediatric population. Glucuronidation mediated by uridine 5′-diphospho-glucuronosyltransferases (UGTs), which possess age-dependent expression, has been proposed as an important metabolic pathway of PTU. To further examine the metabolism of PTU, a reliable HPLC-MS/MS method for the simultaneous quantification of PTU and its N-β-D glucuronide (PTU-GLU) was developed and validated. The chromatographic separation was achieved on a ZORBAX Extend-C18 column (2.1 × 50 mm, 1.8 μm) through gradient delivery of a mixture of formic acid, methanol and acetonitrile. The electrospray ionization (ESI) was operated in its negative ion mode while PTU and PTU-GLU were detected by multiple reaction monitoring (MRM). This analytical method displayed excellent linearity, sensitivity, accuracy, precision, recovery and stability while its matrix effect and carry-over were insignificant. Subsequently, the in vitro metabolism of PTU was assessed and UGT1A9 was identified as an important UGT isoform responsible for the glucuronidation of PTU. The information obtained from this study will facilitate future mechanistic investigation on the hepatoxicity of PTU and may optimize its clinical application.Min LiQingfeng HeLi YaoXiaofeng WangZhijia TangXiao ZhuHai-Shu LinXiaoqiang XiangMDPI AGarticlepropylthiouracilpropylthiouracil glucuronidein vitrohuman liver microsomesUGT1A9HPLC-MS/MSMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1194, p 1194 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	propylthiouracil propylthiouracil glucuronide in vitro human liver microsomes UGT1A9 HPLC-MS/MS Medicine R Pharmacy and materia medica RS1-441
spellingShingle	propylthiouracil propylthiouracil glucuronide in vitro human liver microsomes UGT1A9 HPLC-MS/MS Medicine R Pharmacy and materia medica RS1-441 Min Li Qingfeng He Li Yao Xiaofeng Wang Zhijia Tang Xiao Zhu Hai-Shu Lin Xiaoqiang Xiang Simultaneous Quantification of Propylthiouracil and Its <i>N</i>-β-<span style="font-variant: small-caps">d</span> Glucuronide by HPLC-MS/MS: Application to a Metabolic Study
description	Propylthiouracil (PTU) is commonly prescribed for the management of hyperthyroidism and thyrotoxicosis. Although the exact mechanism of action is not fully understood, PTU is associated with hepatoxicity in pediatric population. Glucuronidation mediated by uridine 5′-diphospho-glucuronosyltransferases (UGTs), which possess age-dependent expression, has been proposed as an important metabolic pathway of PTU. To further examine the metabolism of PTU, a reliable HPLC-MS/MS method for the simultaneous quantification of PTU and its N-β-D glucuronide (PTU-GLU) was developed and validated. The chromatographic separation was achieved on a ZORBAX Extend-C18 column (2.1 × 50 mm, 1.8 μm) through gradient delivery of a mixture of formic acid, methanol and acetonitrile. The electrospray ionization (ESI) was operated in its negative ion mode while PTU and PTU-GLU were detected by multiple reaction monitoring (MRM). This analytical method displayed excellent linearity, sensitivity, accuracy, precision, recovery and stability while its matrix effect and carry-over were insignificant. Subsequently, the in vitro metabolism of PTU was assessed and UGT1A9 was identified as an important UGT isoform responsible for the glucuronidation of PTU. The information obtained from this study will facilitate future mechanistic investigation on the hepatoxicity of PTU and may optimize its clinical application.
format	article
author	Min Li Qingfeng He Li Yao Xiaofeng Wang Zhijia Tang Xiao Zhu Hai-Shu Lin Xiaoqiang Xiang
author_facet	Min Li Qingfeng He Li Yao Xiaofeng Wang Zhijia Tang Xiao Zhu Hai-Shu Lin Xiaoqiang Xiang
author_sort	Min Li
title	Simultaneous Quantification of Propylthiouracil and Its <i>N</i>-β-<span style="font-variant: small-caps">d</span> Glucuronide by HPLC-MS/MS: Application to a Metabolic Study
title_short	Simultaneous Quantification of Propylthiouracil and Its <i>N</i>-β-<span style="font-variant: small-caps">d</span> Glucuronide by HPLC-MS/MS: Application to a Metabolic Study
title_full	Simultaneous Quantification of Propylthiouracil and Its <i>N</i>-β-<span style="font-variant: small-caps">d</span> Glucuronide by HPLC-MS/MS: Application to a Metabolic Study
title_fullStr	Simultaneous Quantification of Propylthiouracil and Its <i>N</i>-β-<span style="font-variant: small-caps">d</span> Glucuronide by HPLC-MS/MS: Application to a Metabolic Study
title_full_unstemmed	Simultaneous Quantification of Propylthiouracil and Its <i>N</i>-β-<span style="font-variant: small-caps">d</span> Glucuronide by HPLC-MS/MS: Application to a Metabolic Study
title_sort	simultaneous quantification of propylthiouracil and its <i>n</i>-β-<span style="font-variant: small-caps">d</span> glucuronide by hplc-ms/ms: application to a metabolic study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a8d10f0df6d343ab9a5a1a043188ee4c
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Simultaneous Quantification of Propylthiouracil and Its <i>N</i>-β-<span style="font-variant: small-caps">d</span> Glucuronide by HPLC-MS/MS: Application to a Metabolic Study

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