Quantitative determination of betamethasone sodium phosphate and betamethasone dipropionate in human plasma by UPLC-MS/MS and a bioequivalence study.
The compound medicine of betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BDP) is widely used for diverse glucocorticoid-sensitive acute and chronic diseases such as asthma, rheumatoid arthritis and systemic lupus erythematosus. It will be useful and beneficial to validate sensitive method for the determination of BSP, BDP and their metabolites for their pharmacokinetic study. Hereby, an ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been validated for the determination of BSP, BDP and their metabolites betamethasone (BOH), betamethasone 17-monodipropionate (B17P) and betamethasone 21-monodipropionate (B21P) in human plasma. Liquid-liquid extraction with ether and n-hexane (v/v, 4:1) was used for sample preparation of BDP, BOH, B17P and B21P with beclomethasone dipropionate as internal standard (IS), while solid phase extraction was adopted for sample preparation of BSP using prednisolone as IS. The chromatographic separation was performed on a Hypurity C18column (150 mm×2.1 mm, 5 μm) for BOH, BDP, B21P and B17P, and a Luna C18(2) column (150 mm×2.0 mm, 5 μm) for BSP. Electrospray ionization interfaced with positive multiple reaction monitoring (MRM) scan mode was used for mass spectrometric detection. The standard calibration curves were linear within the range of 2.525 × 10-9-403.9 × 10-9mol·dm-3for BSP, 0.125 × 10-9-55.81 × 10-9mol·dm-3for BDP, 0.278 × 10-9-74.95 × 10-9mol·dm-3for BOH, 0.098 × 10-9-4.688 × 10-9mol·dm-3for B17P and 0.226 × 10-9-5.411 × 10-9mol·dm-3for B21P, respectively. The validated method was successfully applied to a bioequivalence study in 23 healthy subjects after they were injected with this compound medicine BSP and BDP.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China ; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
Man-Yun
MY
Chen
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China ; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
Yong-Jun
YJ
Tang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China ; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
Yi-Cheng
YC
Wang
Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago; 5841 South Maryland Avenue, MC 4028, Chicago, IL 60637, USA.
Chong-Zhi
CZ
Wang
Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago; 5841 South Maryland Avenue, MC 4028, Chicago, IL 60637, USA.
Chun-Su
CS
Yuan
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China ; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
Yao
Y
Chen
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China ; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
Zhi-Rong
ZR
Tan
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China ; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China ; Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago; 5841 South Maryland Avenue, MC 4028, Chicago, IL 60637, USA.
Wei-Hua
WH
Huang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China ; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
Hong-Hao
HH
Zhou
UPLC-MS; betamethasone; betamethasone dipropionate; betamethasone sodium phosphate; human plasma
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