The need for adequate chromatographic separation in the quantitative determination of drugs in biological samples by high performance liquid chromatography with tandem mass spectrometry

摘要: This work describes real examples of classes drugs (drug candidates) whose quantitative determination in biological matrices by high performance liquid chromatography with electrospray tandem mass spectrometry (LC/MS/MS) may be hampered interferences from drug-related biotransformation products (or prodrugs), unless the chromatographic conditions used achieve separation drug compounds. The investigated include: (a) a lactone drug, open-ring acid as potential product; (b) phenolic and its prodrug; (c) an E-isomer methyloxime Z-isomer (d) carboxylic acylglucuronide (e) thiol disulfide product. For each pair associated compound (except for isomeric pair), full-scan single spectrum gave in-source collisionally induced dissociation (CID) generated fragment ion identical to parent drug. Thus, compound, if present sample, would interfere LC/MS/MS using selected reaction monitoring (SRM) transition LC utilized clearcut compound. bioanalytical methods very short retention times, where there are minimal separations, should only samples which known not contain analyte-related compounds that can undergo SRM determination. Copyright © 1999 John Wiley & Sons, Ltd.