Pharmacokinetic and tissue distribution analysis of bioactive compounds from Fuke Qianjin capsules in rats by a validated UPLCMS/MS method

Abstract

Fuke Qianjin capsules (FKQJ) exhibit obvious advantages and characteristics in the treatment of pelvic inflammatory disease. At present, information regarding the in vivo process of FKQJ is lacking, which has become a bottleneck in further determining the therapeutic effect of this traditional Chinese medicine. In the present study, a sensitive, simple and reliable method was developed and validated for the simultaneous quantification of 12 main components (4 flavonoids, 4 alkaloids, 2 phthalides and 2 diterpene lactones) in plasma and seven tissues of rats to study the pharmacokinetic and distribution characteristics of these components in vivo by using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the first time. Plasma and tissue were prepared by protein precipitation with acetonitrile and methanol, followed by its separation on a Waters Acquity UPLC BEH C₁₈ column. The quantification was performed via multiple reaction monitoring (MRM) by a triple quadrupole mass spectrometer under positive electrospray ionization (ESI) mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect and stability. For 12 analytes, the low limit of quantification (LLOQs) reached 0.005-2.44 ng/mL, and all calibration curves showed good linearity (r² ≥ 0.990) in linear ranges. The intra-day and inter-day precision (relative standard deviation) for all analytes was less than 14.96%, and the accuracies were in the range of 85.29%-114.97%. Extraction recoveries and matrix effects of analytes were acceptable. The pharmacokinetic results showed that the main components could be absorbed quickly, had a short residence time, and were eliminated quickly in vivo. At different time points, the 12 components were widely distributed with uneven characteristics in the body, which tended to be distributed in the liver, kidney and lung and to a lesser extent in the uterus, brain and heart. The pharmacokinetic process and tissue distribution characteristics of FKQJ were expounded in this study, which can provide a scientific theory for in-depth development of FKQJ and guide FKQJ use in the clinic.

Keywords: Fuke Qianjin capsules; Pharmacokinetics; Quantification; Tissue distribution; UPLC-MS/MS.