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Determination of paclitaxel prodrug in SD rat plasma by LC-MS/MS and its application in preclinical pharmacokinetic studies
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Guo-cai WANG, Xiang-yi WANG, Cong-cong XIAO, Jian-peng HUANG, Meng YU, Jiu-ming HE*
Acta Pharmaceutica Sinica | 2022, 57(9) : 2798 - 2804
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Acta Pharmaceutica Sinica | 2022, 57(9): 2798-2804
Original Articles
Determination of paclitaxel prodrug in SD rat plasma by LC-MS/MS and its application in preclinical pharmacokinetic studies
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Guo-cai WANG, Xiang-yi WANG, Cong-cong XIAO, Jian-peng HUANG, Meng YU, Jiu-ming HE*
Affiliations
  • State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, NMPA Key Laboratory for Safety Research and Evaluation of Innovative Drug, Beijing 100050, China
Published: 2022-09-12 doi: 10.16438/j.0513-4870.2022-0381
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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).

paclitaxel  /  prodrug  /  LC-MS/MS  /  preclinical pharmacokinetics
Guo-cai WANG, Xiang-yi WANG, Cong-cong XIAO, Jian-peng HUANG, Meng YU, Jiu-ming HE. Determination of paclitaxel prodrug in SD rat plasma by LC-MS/MS and its application in preclinical pharmacokinetic studies[J]. Acta Pharmaceutica Sinica, 2022 , 57 (9) : 2798 -2804 . DOI: 10.16438/j.0513-4870.2022-0381
Year 2022 volume 57 Issue 9
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Article Info
doi: 10.16438/j.0513-4870.2022-0381
  • Receive Date:2022-03-30
  • Online Date:2025-12-24
  • Published:2022-09-12
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  • Received:2022-03-30
  • Revised:2022-06-23
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    State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, NMPA Key Laboratory for Safety Research and Evaluation of Innovative Drug, Beijing 100050, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
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占总种数比例
Percentage of
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Genus
种数
Number of
species
占总种数比例
Percentage of total
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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