A novel microextraction by packed sorbent–gas chromatography procedure for the simultaneous analysis of antiepileptic drugs in human plasma and urine

Abstract

A simple, accurate, and sensitive microextraction by packed sorbent-gas chromatography-mass spectrometry method has been developed for the simultaneous quantification of four antiepileptic drugs; oxcarbazepine, carbamazepine, phenytoin, and alprazolam in human plasma and urine as a tool for drug monitoring. Caffeine was used as internal standards for the electron ionization mode. An original pretreatment procedure on biological samples, based on microextraction in packed syringe using C(18) as packing material gave high extraction yields (69.92-99.38%), satisfactory precision (RSD < 4.7%) and good selectivity. Linearity was found in the 0.1-500 ng/mL range for these drugs with limits of detection (LODs) between 0.0018 and 0.0036 ng/mL. Therefore, the method has been found to be suitable for the therapeutic drug monitoring of patients treated with oxcarbazepine, carbamazepine, phenytoin, and alprazolam. After validation, the method was successfully applied to some plasma samples from patients undergoing therapy with one or more of these drugs. A comparison of the detection limit with similar methods indicates high sensitivity of the present method over the earlier reported methods. The present method is applied for the analysis of these drugs in the real urine and plasma samples of the epileptic patients.

Clinical Validation and Implications of Dried Blood Spot Sampling of Carbamazepine, Valproic Acid and Phenytoin in Patients with Epilepsy

“…This has prompted us to investigate the applicability of monitoring all three AEDs using only one DBS. Considering the volatile nature of VPA and previous success in quantitation of CBZ and PHT using gas chromatography mass spectrometry (GCMS) [16], GCMS was ultimately chosen as the analytical tool for simultaneous determination of these AEDs. This study was conducted with the main objective of comparing the newly developed GCMS assay with the conventional immunoturbimetric assays.…”

A fully validated method for the determination of lacosamide in human plasma using gas chromatography with mass spectrometry: Application for therapeutic drug monitoring

“…This optimization is usually based on the determination of these drugs, which are included in the regimen, in plasma samples for TDM purposes. For these purposes, GC or LC methods are commonly used for the simultaneous determination of different antiepileptic drugs . To our knowledge, the developed method is the first validated GC–MS method for the determination of lacosamide in human plasma.…”

“…In the pretreatment step of biological samples, the previous studies have used mainly LLE or direct injection after protein precipitation . The direct injected samples after protein precipitation are mainly used for LC analysis and they usually show high matrix effect and significant signal suppression . The development of a sufficient extraction procedure of lacosamide from human plasma was considered necessary for a reliable GC–MS analysis.…”

Development of an analytical method coupling cell membrane chromatography with gas chromatography–mass spectrometry via microextraction by packed sorbent and its application in the screening of volatile active compounds in natural products

“…Methanol can readily permeate the silane sorbent that is enriched with analyte from the aqueous eluate. In studies describing the determination of drugs in plasma and urine by MEPS-GC, methanol showed better elution efficiency than other organic solvents [30,31].…”