Simultaneous determination of five bioactive components of XiaoJin Capsule in normal and mammary gland hyperplasia rat plasma using LC–MS/MS and its application to a pharmacokinetic study

Abstract XiaoJin Capsule (XJC) is a classic Traditional Chinese Medicine formula for clinical treatment of thyroid nodules, mammary gland hyperplasia and breast cancer. For the specification and rational application of XJC in the future, an accurate and specific LC–MS/MS method was developed and validated for quantitative determination of five components in rat plasma after oral administration of XJC. The collected plasma samples were extracted by protein precipitation with methanol–acetonitrile (1:3, v/v) mixture solvent and separated on a C 18 column using a gradient elution system. Mass spectrometry was performed on a triple quadrupole mass spectrometer, and samples were detected in positive ionization and multiple reactions monitoring mode. The method was properly validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves showed good linearity ( r 2 > 0.9910) over their concentration ranges. The intra‐ and inter‐day precisions (RSD) were within 11.0%, and the LLOQ was 0.1, 0.2, 0.5, 7.5 and 7.5 ng/ml for aconine, songorine, neoline, 3‐acetyl‐11‐keto‐ β ‐boswellic acid and 11‐keto‐ β ‐boswellic acid, respectively. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. This established method was successfully applied to a pharmacokinetics study of five compounds after oral administration of XJC to normal and mammary gland hyperplasia model rats.