Measurement of Mycophenolic Acid and Its Glucuronide in the Plasma and Study on Gender-related Pharmacokinetics Based on UGTs Enzymes
10.13748/j.cnki.issn1007-7693.20222835
- VernacularTitle:霉酚酸与代谢物的血药浓度测定及基于UGTs酶的性别相关的药动学研究
- Author:
WU Lili
1
,
2
;
XIA Chen
1
,
2
;
LI Qiaoxi
1
,
2
;
LIU Bihao
3
;
ZHANG Hongyu
1
,
2
;
WANG Yan
1
,
2
Author Information
1. Department of Pharmacy, The First People'
2. s Hospital of Foshan, Foshan 528000, China
3. Foshan Blink Biomedical Research Co., Ltd., Foshan 528251, China
- Publication Type:Journal Article
- Keywords:
mycophenolic acid;
mycophenolic acid glucuronide;
UGTs;
gender difference
- From:
Chinese Journal of Modern Applied Pharmacy
2023;40(19):2659-2664
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To establish a UPLC detection method for simultaneous determination of mycophenolic acid(MPA) and its glucuronide(MPAG) in plasma of rats, and to investigate gender-related pharmacokinetic characteristics of mycophenolic acid. METHODS Twelve SD rats(half male and half female) were intragastrically administrated with 90 mg·kg-1·d-1mycophenolate acetate, and blood was collected from periorbital vein at different time points after administration. Plasma samples were extracted by liquid-liquid extraction and drug concentrations of MPA and metabolite MPAG in plasma were determined using UPLC. The method was developed using Waters BEH C18 column. The gradient elution was performed at a flow rate of 0.35 mL·min-1 with the mobile phase acetonitrile solution (A)-0.1% formic acid aqueous solution(B). The detection wavelength was at 266 nm and column oven temperature was maintained at 40 ℃. The pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS The linear relationship between peak area and concentrations of MPA and MPAG were good in the ranges of 0.31-160 µg·mL-1(R2=0.999 8) and 0.62-320 µg·mL-1(R2=0.999 4), respectively. Analytical methods of MPA and MPAG all met the requirements of the methodology. Pharmacokinetic parameters AUC0-t and Cmax of MPA and MPAG in female rats were higher than that in male rats(P<0.05 or P<0.01). In addition, the metabolic rate of genistein[UDP-glucuronosyltransferases(UGT)s substrate] and MPA in male rat liver microsomes were significantly faster than that in female rat liver microsomes. CONCLUSION This developed UPLC method is sensitive, accurate and specific, which is suitable to detect the concentrations of MPA and MPAG in the plasma. The pharmacokinetics of MPA and MPAG in rats are gender different, which may be related to the sex difference of UGTs metabolic enzyme activity.
