Simultaneous quantification of atractyloside and carboxyatractyloside in rat plasma by LC‐MS/MS: Application to a pharmacokinetic study after oral administration of Xanthii Fructus extract

Abstract

Xanthii Fructus is extensively used as an herbal medicine. Ingestion of this herb is associated with severe hepatotoxicity and nephrotoxicity. Atractyloside and carboxyatractyloside are two dominative toxic constituents in Xanthii Fructus. However, their pharmacokinetic study is lacking. In this study, a novel high-performance liquid chromatography-tandem mass spectrometry method was developed to simultaneously quantify the rat plasma concentrations of atractyloside and carboxyatractyloside. After protein precipitation, the analytes were chromatographic separated on a ZORBAX Eclipse Plus column (2.1 × 150 mm id, 5 µm) under gradient elute. In the negative electrospray ionization mode, the transitions at m/z 725.3→645.4 for atractyloside, m/z 769.3→689.4 for carboxyatractyloside, and m/z 479.2→121.1 for paeoniflorin (the internal standard) were acquired by multiple reaction monitoring. This analytical method showed good linearity over 1-500 ng/mL for atractyloside and 2-500 ng/mL for carboxyatractyloside with acceptable precision and accuracy. No matrix effect, instability and carryover occurred in the analysis procedure. The extraction recoveries were greater than 85.0%. This method was applied to a preliminary pharmacokinetic study by orally administering Xanthii Fructus extract (9 g/kg) to rats, which was useful to evaluate the role of these two compounds in Xanthii Fructus-induced toxicity. K E Y W O R D Satractyloside, carboxyatractyloside, mass spectrometry, pharmacokinetics, Traditional Chinese medicine 590

Direct and indirect targets of carboxyatractyloside, including overlooked toxicity toward nucleoside diphosphate kinase (NDPK) and mitochondrial H + leak

“…Curiously, ATR and CATR display comparable properties in terms of their absorption rate and elimination half-life (studies using rats) (Pan et al. 2020 ). However, the contents of these glycosides and their proportions in crude versus processed herbal material may considerably differ and are related to the geographical location (effects of climate and soil composition), harvesting time (effects of aging and desiccation), and genetic factors (Santi 1958 ; Obatomi and Bach 1998 ; Daniele et al.…”

“…2020 ; Pan et al. 2020 ). Additionally, variation in sampling and detection methods explains the incredibly large discrepancies in the ATR/CATR concentrations among the different parts of a tested plant (described above for Xanthium spp.)…”

Simultaneous determination of nine tyrosine kinase inhibitors in three complex biological matrices by using high‐performance liquid chromatography–diode array detection combined with a second‐order calibration method

“…It has been reported that the simultaneous analysis of the above nine TKIs using HPLC–diode array detection (DAD) required a running time of 17.5–35 min [8–11]. LC–MS and LC–MS/MS have high analytical SEN [12–14]. However, they are expensive, have high maintenance costs, and need professional technicians to operate.…”