A simple and sensitive LC–MS/MS method for the determination of polyphyllin VII in rat plasma and its application to pharmacokinetic study

Abstract

Polyphyllin VII is an isoprene saponin extracted from Rhizoma paridis, and it can effectively suppress tumor initiation, growth, and metastasis. In this study, we aim to develop and validate an LC-MS/MS method for the quantification of polyphyllin VII in rat plasma using digoxin as the internal standard (IS). The plasma samples were precipitated with methanol, and the samples were separated on an ACQUITY BEH C 18 column (2.1 Â 50 mm, 1.7 μm). The mobile phase consisted of 0.1% formic acid solution and acetonitrile. The detection was performed in the multiple reactions monitoring mode, with the precursor-to-product transitions of m/z 1075.4 > 883.3 for polyphyllin VII and m/z 779.4 > 649.6 for the IS. The method showed excellent linearity over the concentration range of 0.5-1000 ng/ml, with a correlation coefficient of 0.9996 (r = 0.9996). The lower limit of quantification was 0.5 ng/ml. The inter-and intra-day accuracy (relative error) ranged from À4.8 to 5.9%, and precision (relative standard deviation) was < 9.0%. The assay showed high extraction recovery, ranging from 90.6 to 95.6%. Polyphyllin VII was demonstrated to be stable under the storage conditions. The validated LC-MS/MS method was successfully applied to the pharmacokinetic study of polyphyllin VII in rats after oral, intraperitoneal, and intravenous administrations. The pharmacokinetic results indicated that polyphyllin VII showed low oral (5.86%) bioavailability and moderate (38.81%) intraperitoneal bioavailability.

Polyphyllin VII induces autophagy‐dependent ferroptosis in human gastric cancer through targeting T‐lymphokine‐activated killer cell‐originated protein kinase

“…At an in vivo dose of 1/20 of LD 50 (2 mg/kg), PPVII had no significant effect on the liver, spleen, and kidney functions of nude mice, which indicated that PPVII had little toxicity in vivo. According to our previous papers and other reports about the pharmacokinetic data of PPVII in SD rats, the bioavailability of oral administration of PPVII is much lower than that of intraperitoneal administration, and has low gastrointestinal absorption or overhead metabolic problems (H. Wang et al, 2023). Thus, current animal study only used one mode of intraperitoneal injection.…”