Determination of paclitaxel prodrug in SD rat plasma by LC-MS/MS and its application in preclinical pharmacokinetic studies
10.16438/j.0513-4870.2022-0381
- VernacularTitle:LC-MS/MS法测定SD大鼠血浆中紫杉醇前药含量及其在临床前药代动力学研究中的应用
- Author:
Guo-cai WANG
;
Xiang-yi WANG
;
Cong-cong XIAO
;
Jian-peng HUANG
;
Meng YU
;
Jiu-ming HE
- Publication Type:Research Article
- Keywords:
paclitaxel;
prodrug;
LC-MS/MS;
preclinical pharmacokinetics
- From:
Acta Pharmaceutica Sinica
2022;57(9):2798-2804
- CountryChina
- Language:Chinese
-
Abstract:
A fast and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of prodrug of paclitaxel (Pro-PTX) and paclitaxel (PTX) in rat plasma was developed. The plasma samples were subjected to protein precipitation with acetonitrile (0.1% formic acid), and then separated by LC with an Ultimate AQ-C18 column (50 mm × 3.0 mm, 3 μm) and acetonitrile-1 mmol·L-1 ammonium formate (containing 0.1% formic acid) as the mobile phase. Multiple reaction monitoring (MRM) scanning mode was used to detect the ion responses m/z 983.4→415.2 (Pro-PTX), m/z 854.4→286.1 (PTX) and m/z 808.3→527.2 (Docetaxel, internal standard) by using a triple quadrupole tandem mass spectrometer with electrospray ionization source and positive ion mode. The method validation results show that the linear ranges of Pro-PTX and PTX in plasma were 2.00-500 ng·mL-1 (r > 0.99) and 4.00-1 000 ng·mL-1 (r > 0.99), the lower limit of quantification was 2.00 ng·mL-1 and 4.00 ng·mL-1, respectively; the quality control samples with low, medium and high concentrations of Pro-PTX and PTX were within the batch, the relative standard deviation (RSD) between batches were all less than 9%; the relative deviation (RE) was within the range of ± 9%; In the stability test, both Pro-PTX and PTX in plasma were stable under various storage conditions. The method was sensitive, specific, and reproducible, and was suitable for the pharmacokinetic study of Pro-PTX in rats. Animal experiments were approved by the Ethics Committee of Laboratory Animal Management and Animal Welfare, Institute of Materia Medica, Chinese Academy of Medical Sciences (No.: 00003552).
