Simultaneous determination of tanshinones and polyphenolics in rat plasma by UPLC-MS/MS and its application to the pharmacokinetic interaction between them

• Published in: Drug testing and analysis 2016-07, Vol.8 (7), p.744-754
• Main Authors: Ren, Hao, Qian, Dawei, Su, Shulan, Guan, Hanliang, Zhang, Wei, Shang, Erxin, Duan, Jinao
• Format: Article
• Language: English
• Subjects: Abietanes - blood; Animals; Benzaldehydes - blood; Benzofurans - blood; Bioavailability; Catechols - blood; Chromatography, High Pressure Liquid - methods; Cinnamates - blood; Depsides - blood; Drug testing; Ions; Lactates - blood; Limit of Detection; Liquid-Liquid Extraction - methods; Male; pharmacokinetic interaction; Pharmacokinetics; Phenanthrenes - blood; Plasma; polyphenolics; Polyphenols - blood; Rats, Sprague-Dawley; Rosmarinic Acid; Saliva miltiorrhiza Bunge; Tandem Mass Spectrometry - methods; tanshinones; UPLC-MS/MS
• ISSN: 1942-7603; 1942-7611
• DOI: 10.1002/dta.1840

The aim of this study was to investigate the pharmacokinetic interaction between tanshinones and polyphenolics which act as the main bioactive compounds in Saliva miltiorrhiza Bunge (SMB). Thus, a rapid and highly sensitive ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) method was developed and validated to determine the concentrations of Tanshinone IIA (TSIIA), Tanshinone I (TI), Cryptotanshinone (CT), Salvianolic acid B (Sal B), Protocatechuic aldehyde (PAL), Rosmarinic acid (RA), and Danshensu (DSS) in rat plasma. The Sprague–Dawley rats were allocated to three groups which orally administered tanshinones (DST), polyphenolics (DFS), and a mixture of tanshinones and polyphenolics (DTF). These samples were processed by a simple liquid‐liquid extraction (LLE) method with ethyl acetate. Chromatographic separation was achieved on an Acquity BEH C18 column (100 mm × 2. 1 mm, 1.7 µm) with the mobile phase consisting of 0.1% (v/v) formic acid and acetonitrile by gradient elution at a flow rate of 0.4 mL/min. The detection was performed on a triple quadrupole‐tandem mass spectrometer TQ‐MS/MS equipped with negative and positive electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) mode. The statistical analysis was performed by the Student's t‐test with P ≤ 0.05 as the level of significance. The method showed good precision, accuracy, recovery, sensitivity, linearity, and stability. The pharmacokinetic profiles and parameters of these polyphenolics changed when co‐administrated with tanshinones. The tanshinones improved the bioavailability of DSS, accelerated the eliminating rate of RA and Sal B and promoted their distribution in vivo. They also contributed to promoting the biotransformation of Sal B to DSS. The polyphenolics could affect the pharmacokinetic of tanshinones, especially CT and TSIIA. Furthermore, the biotransformation of CT to TSIIA and the bioavailability of TSIIA were both improved. This study may provide useful information to avoid unexpected increase of the plasma drug concentration in the clinical practice. Copyright © 2015 John Wiley & Sons, Ltd. This paper developed a rapid, selective and specific LC‐MS/MS method for simultaneous analysis of four polyphenolics and three tanshinones. The analytical procedure was successfully applied to investigate the pharmacokinetic interaction between these two kinds of compounds in SD rats. The results showed change pharmacokinetic parameters when co‐