Development and Validation of a Rapid and Specific UHPLC–MS/MS Method for Simultaneous Determination of 21 Bioactive Components in Tiantai No. 1 Pill and Rat Plasma

Abstract

Tiantai No. 1, as a hospital Chinese materia medica preparation, has been used in the treatment of mild cognitive impairment and Alzheimer disease for nearly 20 years. It is composed of six herbal medicines: Panax Ginseng, Coptidis Rhizoma, Evodiae Fructus, Cistanches Herba, Curcuma Longa Rhizoma and Borneol. So far, lots of studies have been carried out on the pharmacodynamics but few on quality evaluation and pharmacokinetic study of Tiantai No. 1. A novel method of ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) developed to determine the concentrations of 21 bioactive components, including Ginsenoside Rg1, Rb1, Rd, Berberine, Epiberberine, Jatrorrhizine, Palmatine, Columbamine, Coptisine, Evodiamine, Dehydroevodiamine, Rutaecarpine, Limonin, Hyperin, Curcumin, Demethoxycurcumin, Bisdemethoxycurcumin, Geniposidic acid, Echinacoside, Isoacteoside and Verbascoside in Tiantai No. 1 and rat plasma is essential for further research. The separation by UHPLC was performed on an Agilent Zorbax Eclipse Plus C18 column (4.6 mm × 150 mm, 3.5 μm) at a flow rate of 0.4 mL min−1 using acetonitrile and 0.1%(v/v) formic acid aqueous solution as mobile phase. Mass spectrometric detection was performed on multiple reaction monitoring (MRM) in either positive or negative ionization mode. The established method was validated and showed good linearity (r2 > 0.9994), sensitivity (LLOQ among 1.000–2.200 ng mL−1), precision (RSD value among 0.81–12.51%), stability (RSD value less than 4.59%) and repeatability (RSD value less than 4.07%). The mean recoveries ranged from 93.12 to 100.25% with SD value less than 4.97%. Moreover, this proposed method was successfully utilized for simultaneous determination of 21 bioactive components in Tiantai No. 1 and rat plasma samples. Results showed that this proposed method was beneficial for quality standard improvement and further pharmacokinetic research of Tiantai No. 1.