Pharmacokinetics and Tissue Distribution Study of Modified Xiaochaihu Granules Against Gastric Ulcer Induced by Ethanol in Rats by UPLC-MS/MS

Abstract

Gastric ulcer (GU) is one of the major gastrointestinal disorder diseases, with increasing incidence and prevalence globally. Modified Xiaochaihu granules (MXCHG) have been used effectively for treating chronic gastritis and GU clinically. To investigate the pharmacokinetics and tissue distribution of MXCHG, an ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method was established for the simultaneous determination of 8 bioactive ingredients (baicalin, wogonoside, baicalein, liquiritin, glycyrrhizic acid, berberine hydrochloride, saikosaponin a, and saikosaponin d) in rat plasma and various tissues using puerarin as an internal standard (IS). The biological samples were pretreated by protein precipitation with acetonitrile. The chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of acetonitrile and 0.1% formic acid in water. All analytes and IS were quantitated through ESI in the positive/negative ion multiple reaction monitoring mode. The mass transitions were as follows: m/z 445.0 → 268.5 for baicalin, m/z 458.7 → 282.8 for wogonoside, m/z 269.2 → 222.6 for baicalein, m/z 417.0 → 254.8 for liquiritin, m/z 822.1 → 350.8 for glycyrrhizic acid, m/ z 336.0 → 319.9 for berberine hydrochloride, m/z 780.3 → 618.5 for saikosaponin, and m/z 415.0 → 294.6 for the IS. The validated method was successfully applied to the pharmacokinetics and tissue distribution study of 8 compounds in rat plasma and tissues after the intragastric administration of MXCHG. The results demonstrated that 8 components were distributed widely and rapidly in various rat tissues after intravenous administration. Tissue deposition of the compounds in the rats was mainly in the small intestine and stomach. The present study can provide more useful information to guide the clinical use of MXCHG and the developed analytical method can also be applied for further clinical pharmacokinetic studies.