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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MDPI AG
2021-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/11/1194 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:10:14Z |
| format | Article |
| id | doaj.art-a8d10f0df6d343ab9a5a1a043188ee4c |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T05:10:14Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-a8d10f0df6d343ab9a5a1a043188ee4c2023-11-23T00:56:41ZengMDPI AGPharmaceuticals1424-82472021-11-011411119410.3390/ph14111194Simultaneous 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 StudyMin Li0Qingfeng He1Li Yao2Xiaofeng Wang3Zhijia Tang4Xiao Zhu5Hai-Shu Lin6Xiaoqiang Xiang7Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, ChinaDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, ChinaDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, ChinaDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, ChinaDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, ChinaDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, ChinaCollege of Pharmacy, Shenzhen Technology University, Shenzhen 518118, ChinaDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, ChinaPropylthiouracil (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.https://www.mdpi.com/1424-8247/14/11/1194propylthiouracilpropylthiouracil glucuronidein vitrohuman liver microsomesUGT1A9HPLC-MS/MS |
| spellingShingle | 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 Pharmaceuticals propylthiouracil propylthiouracil glucuronide in vitro human liver microsomes UGT1A9 HPLC-MS/MS |
| 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_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_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_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 |
| topic | propylthiouracil propylthiouracil glucuronide in vitro human liver microsomes UGT1A9 HPLC-MS/MS |
| url | https://www.mdpi.com/1424-8247/14/11/1194 |
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