Pharmacokinetic study of scutellarin in healthy volunteers by enzymatic hydrolysis and LC-MS-MS analysis / 中国药理学通报

ABSTRACT

Aim To establish a combined method ofβ-glucuronidase hydrolysis and LC-MS-MS analysis for the determination of scutellarein in human plasma, and investigate the pharmacokinetics of scutellarin prepara-tion in healthy male volunteers. Methods Plasma samples were prepared by enzymolysis with β-glucu-ronidase and protein precipitation with methanol. The analytes scutellarein and quercetin ( IS ) were separa-ted on an Agilent ZORBAX SB C18 column ( 2. 1 mm × 150 mm, 5 μm) with the mobile phases consisting of acetonitrile, methanol and water. Multiple reaction monitoring ( MRM) on MS was used to monitor precur-sor to produce ion transitions of m/z 285. 0→136. 8 for scutellarein and m/z 301. 1→120. 8 for IS. After method validation, this method was applied to deter-mine the plasma concentration of scutellarein in 12 male volunteers following single oral administration of 120 mg scutellarin preparation. Drug And Statistic soft-ware (1. 0) was used to process data and the pharma-cokinetic parameters were calculated. Results The assay was validated with linear range of 4 . 01-513. 38μg · L-1 for scutellarein. The intra- and inter-batch precisions ( RSD%) were within 7. 22%. The absolute recoveries were more than 84. 23%. The pharmacoki-netic parameters after a single dose were as followsCmax (μg · L-1 ) 159. 97 ± 58. 14; AUC(0-19) (μg · L-1·h)1151. 37 ±279. 80; AUC(0-∞)(μg·L-1· h)1194. 13 ± 264. 51; Tmax ( h)6. 33 ± 1. 67; T1/2 (h)2. 83 ± 0. 60. Conclusion The assay method is proved to be sensitive, accurate and convenient. It can be successfully applied to a pharmacokinetic study of scutellarin in healthy male volunteers.