Analysis of drugs in plasma samples from schizophrenic patients by column-switching liquid chromatography-tandem mass spectrometry with organic–inorganic hybrid cyanopropyl monolithic column

• Development of the selective organic–inorganic hybrid cyanopropyl monolithic for bioanalysis.
• This capillary was reused more than 100 times as sorbent for column-switching.
• The high permeability of the monolithic capillary facilitated the biological sample percolation.
• Column-switching LC-MS/MS system for therapeutic drug monitoring in patients with schizophrenia.
• The column-switching LC-MS/MS method presented LLOQs values at sub-therapeutic levels.

This study reports on the development of a rapid, selective, and sensitive column-switching liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to analyze sixteen drugs (antidepressants, anticonvulsants, anxiolytics, and antipsychotics) in plasma samples from schizophrenic patients. The developed organic-inorganic hybrid monolithic column with cyanopropyl groups was used for the first dimension of the column-switching arrangement. This arrangement enabled online pre-concentration of the drugs (monolithic column) and their subsequent analytical separation on an XSelect SCH C18 column. The drugs were detected on a triple quadrupole tandem mass spectrometer (multiple reactions monitoring mode) with an electrospray ionization source in the positive ion mode. The developed method afforded adequate linearity for the sixteen target drugs; the coefficients of determination (R2) lay above 0.9932, the interassay precision had coefficients of variation lower than 6.5%, and the relative standard error values of the accuracy ranged from −14.0 to 11.8%. The lower limits of quantification in plasma samples ranged from 63 to 1250 pg mL−1. The developed method successfully analyzed the target drugs in plasma samples from schizophrenic patients for therapeutic drug monitoring (TDM).