An Effective and Sensitive HPLC-MS/MS Method for Determination of Cholic Acid-Coupled Camptothecin Derivative A2 in Rat Pharmacokinetics and Tissue Distribution

Camptothecin bile acid analog (A2) is a camptothecin derivative, which has been verified to possess the high anti-tumor activity. The purpose of this study was to develop an effective and sensitive detection method to investigate the pharmacokinetics, tissue distributions and the bioavailability in rat plasma and other organs for the further understanding of A2. The standard curves, control samples and quality control samples were prepared by blank plasma and tissues of non-administered mice at 4 degrees C for HPLC-MS/MS analysis. The method validation was carried out on the five different occasions (specificity and selectivity, linearity, accuracy and precision, extraction recovery and matrix effects, and stability). The pharmacokinetic analysis showed that A2 showed twice absorption at 1 h and 4 h after oral administration and the second absorption was stronger than the first absorption. A2 was distributed mainly in the intestine and spleen. A2 had great oral bioavailability and the potential targeting property, indicating that CPT coupled to bile acid groups helped to improve bioavailability by bile acid transporters. These results would promote the development of camptothecin-bile acid analogue.