Time-course monitoring of in vitro biotransformation reaction via solid-phase microextraction-ambient mass spectrometry approaches  

作　　者：Karol Jaroch Janusz Pawliszyn 

机构地区：[1]Department of Chemistry,University of Waterloo,Waterloo,N2L 3G1,Canada [2]Department of Pharmacodynamics and Molecular Pharmacology,Faculty of Pharmacy,Collegium Medicum in Bydgoszcz,Nicolaus Copernicus University in Toruń Poland,85090,Bydgoszcz,Poland

出　　处：《Journal of Pharmaceutical Analysis》2022年第1期186-191,共6页药物分析学报（英文版）

基　　金：supported by Shimadzu Scientific Instruments(Columbia,MD,USA)and Canada’s National Science and Engineering Research Council-Industrial Research Chair(NSERC-IRC)program,grant number IRCPJ 184412-15

摘　　要：The solid-phase microextraction technique quantifies analytes without considerably affecting the sample composition.Herein,a proof-of-concept study was conducted to demonstrate the use of coated probe electrospray ionization(coated-PESI)and coated blade spray(CBS)as ambient mass spectrometry approaches for monitoring drug biotransformation.The ability of these methods was investigated for monitoring the dephosphorylation of a prodrug,combretastatin A4 phosphate(CA4P),into its active form,combretastatin A4(CA4),in a cell culture medium supplemented with fetal bovine serum.The CBS spot analysis was modified to achieve the same extraction efficiency as protein precipitation and obtained results in 7 min.Because coated-PESI performs extraction without consuming any samples,it is the preferred technique in the case of a limited sample volume.Although coated-PESI only extracts small quantities of analytes,it uses the desorption solvent volume of 5-10 pL,resulting in high sensitivity,thus allowing the detection of compounds after only 1 min of extraction.The biotransformation of CA4P into CA4 via phosphatases occurs within the simple matrix,and the proposed sample preparation techniques are suitable for monitoring the biotransformation.

关 键 词：Solid-phase microextraction Coated probe electrospray ionization Coated blade spray COMBRETASTATIN BIOTRANSFORMATION Prodrug activation 

分 类 号：R914[医药卫生—药物化学]