Determination and pharmacokinetics investigation of prodrugs of paclitaxel fatty acid esters in mouse plasma by UPLC-MS/MS
10.12206/j.issn.2097-2024.202404082
- VernacularTitle:UPLC-MS/MS法测定小鼠血浆中紫杉醇脂肪酸酯前药及其药代动力学研究
- Author:
Bingchen CHEN
1
;
Dafeng TONG
1
;
Miao WAN
1
;
Feihu YAN
1
;
Jianzhong YAO
2
Author Information
1. Department of Colorectal Surgery, the First Affiliated Hospital.
2. Department of Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai, 200433, China.
- Publication Type:Originalarticles
- Keywords:
Paclitaxel;
Fatty acid esters;
Prodrug;
UPLC-MS/MS;
Pharmacokinetics
- From:
Journal of Pharmaceutical Practice and Service
2024;42(8):341-345
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish an UPLC-MS/MS method for determinating content of three paclitaxel fatty acid esters such as paclitaxel myristate （PTX-MA）, paclitaxel palmitate （PTX-PA） and paclitaxel myristate （PTX-SA） in mouse plasma, and preliminarily investigate the pharmacokinetic characteristics of their liposomes in mice. Methods Eclipse Plus C8 chromatography column （2.1 mm×50 mm, 1.8 μm） was used with different proportions of 0.2% formic acid aqueous solution （A） and methanol （B） mixture as mobile phase for gradient elution at a flow rate of 0.3 ml/min. The collum temperature was 30℃. The sample injection volume was 10 μl. The triple quadrupole mass series spectrometer was used as multi-reaction monitoring （MRM）. Results PTX-MA, PTX-PA and PTX-SA all exhibited a good linear relationship in the range of 5.0~500.0 ng/ml （r>0.9950）. Their RSD of precision, stability, extraction recovery rate and matrix effect test results was all less than 10%. The half-lives （t1/2） for liposomes of three paclitaxel fatty acid esters PTX-MA-L、PTX-PA-L and PTX-SA-L in mice were 14.78 h, 44.49 h and 69.32 h individually, and their clearance rates （CL） were 29.06 L·kg/h, 24.94 L·kg/h and 13.74 L·kg/h, respectively. Conclusion This method had high specificity, sensitivity, easy operation and good stability, which could be used for the determination of paclitaxel fatty acid esters in mouse plasma. The results of pharmacokinetic studies in mice showed that t1/2 for paclitaxel fatty acid esters were significantly prolonged, and the clearance rate were significantly reduced with the length of fatty acid carbon chains increasement, which indicated that esterification of paclitaxel with different chain length saturated fatty acids could obviously alter its in vivo pharmacokinetic properties, which provided scientific basis for the research and development of nano formulations of paclitaxel fatty acid ester prodrug.
