Time-course monitoring of in vitro biotransformation reaction via solid-phase microextraction-ambient mass spectrometry approaches
- Author:
Jaroch KAROL
1
,
2
;
Pawliszyn JANUSZ
Author Information
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 Torun Poland,85090,Bydgoszcz,Poland
- Keywords:
Solid-phase microextraction;
Coated probe electrospray ionization;
Coated blade spray;
Combretastatin;
Biotransformation;
Prodrug activation
- From:
Journal of Pharmaceutical Analysis
2022;12(1):186-191
- CountryChina
- Language:Chinese
-
Abstract:
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 ap-proaches 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 ob-tained 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.
