Meiyun Shi1,2, Lei Yin1,2, Yantong Sun3, Can Wang1, Lanlan Cai1, Tinglan Zhang1, Xiaotong Zhou1, J Paul Fawcett1, Xiaoli Gao4,5,6, Jingkai Gu7. 1. Research Center for Drug Metabolism, School of Life Science, Jilin University, 2699 Qianjin Street, Changchun, 130012, People's Republic of China. 2. School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, People's Republic of China. 3. School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China. 4. College of Pharmacy, Xinjiang Medical University, Urumqi, 830011, People's Republic of China. xli_g@sina.com. 5. Xinjiang Key Laboratory of Active Components and Drug Release Technology of Natural Drugs, Urumqi, People's Republic of China. xli_g@sina.com. 6. Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, Beijing, People's Republic of China. xli_g@sina.com. 7. Research Center for Drug Metabolism, School of Life Science, Jilin University, 2699 Qianjin Street, Changchun, 130012, People's Republic of China. gujk@jlu.edu.cn.
Abstract
BACKGROUND AND OBJECTIVE: Postmenopausal women often require estrogen supplementation to improve menopausal and postmenopausal vasomotor symptoms and maintain hormonal balance. Conjugated equine estrogens extracted from the urine of pregnant mares are commonly used to provide this estrogen replacement therapy. The complex composition of this mixture of animal sulfated metabolites makes its bioanalysis challenging such that its detailed pharmacokinetics has not been fully characterized. The purpose of this work is to reveal the pharmacokinetic behavior of conjugated equine estrogens in healthy Chinese postmenopausal women by a parallel two-column LC-MS/MS method. METHODS: An open-label study was carried out in 35 Chinese healthy postmenopausal women who received a single dose of Premarin® 0.625 mg. A high-throughput column-switching liquid chromatography-tandem mass spectrometry method was developed to determine four conjugated estrogens and two unconjugated estrogens formed by hydrolysis in vivo. The method multiplexes two high-performance liquid chromatography systems into one mass spectrometer and incorporates the positive/negative ion switching acquisition mode of mass spectrometry to significantly increase analysis efficiency. Pharmacokinetics was determined using non-compartmental methods. RESULTS: Both conjugated and unconjugated estrogens can be analyzed simultaneously in a single run with an analysis time of 13.0 minutes in the column-switching liquid chromatography-tandem mass spectrometry method as opposed to 23.0 minutes in a single-column liquid chromatography-tandem mass spectrometry system. The exposures (maximum concentration and area under the curve) of estrone and equilin in Chinese women were higher than those in the North American women. CONCLUSIONS: The fully validated assay was successfully applied to a pharmacokinetic study in healthy postmenopausal Chinese women after oral administration of a conjugated equine estrogen tablet. This study suggests that Chinese postmenopausal women achieve the same level of unconjugated estrogens in plasma at a lower dose of conjugated equine estrogens than North American women.
BACKGROUND AND OBJECTIVE: Postmenopausal women often require estrogen supplementation to improve menopausal and postmenopausal vasomotor symptoms and maintain hormonal balance. Conjugated equine estrogens extracted from the urine of pregnant mares are commonly used to provide this estrogen replacement therapy. The complex composition of this mixture of animal sulfated metabolites makes its bioanalysis challenging such that its detailed pharmacokinetics has not been fully characterized. The purpose of this work is to reveal the pharmacokinetic behavior of conjugated equine estrogens in healthy Chinese postmenopausal women by a parallel two-column LC-MS/MS method. METHODS: An open-label study was carried out in 35 Chinese healthy postmenopausal women who received a single dose of Premarin® 0.625 mg. A high-throughput column-switching liquid chromatography-tandem mass spectrometry method was developed to determine four conjugated estrogens and two unconjugated estrogens formed by hydrolysis in vivo. The method multiplexes two high-performance liquid chromatography systems into one mass spectrometer and incorporates the positive/negative ion switching acquisition mode of mass spectrometry to significantly increase analysis efficiency. Pharmacokinetics was determined using non-compartmental methods. RESULTS: Both conjugated and unconjugated estrogens can be analyzed simultaneously in a single run with an analysis time of 13.0 minutes in the column-switching liquid chromatography-tandem mass spectrometry method as opposed to 23.0 minutes in a single-column liquid chromatography-tandem mass spectrometry system. The exposures (maximum concentration and area under the curve) of estrone and equilin in Chinese women were higher than those in the North American women. CONCLUSIONS: The fully validated assay was successfully applied to a pharmacokinetic study in healthy postmenopausal Chinese women after oral administration of a conjugated equine estrogen tablet. This study suggests that Chinese postmenopausal women achieve the same level of unconjugated estrogens in plasma at a lower dose of conjugated equine estrogens than North American women.
Authors: Paulo Roberto Stevanato Filho; Samuel Aguiar Júnior; Maria Dirlei Begnami; Fábio de Oliveira Ferreira; Wilson Toshihiko Nakagawa; Ranyell Matheus Sobreira Batista Spencer; Tiago Santoro Bezerra; Philip Edward Boggiss; Ademar Lopes Journal: Pathol Oncol Res Date: 2017-07-05 Impact factor: 3.201
Authors: Lorna C Gilligan; Habibur P Rahman; Anne-Marie Hewitt; Alice J Sitch; Ali Gondal; Anastasia Arvaniti; Angela E Taylor; Martin L Read; Dion G Morton; Paul A Foster Journal: J Clin Endocrinol Metab Date: 2017-12-01 Impact factor: 5.958