Validated LC–MS/MS method for the determination of some prescribed CNS drugs: Application to an in vivo pharmacokinetic study of drug-herb metabolic interaction potential of khat

Abstract

The consumption of khat (Catha edulis), a natural amphetamine-like psychostimulant plant, during co-administration of other conventional medications may alter treatment outcomes. Therefore, in this in-vivo study, we investigated the effect of concomitant co-administration of Khat on the pharmacokinetics of some prescribed CNS drugs: clomipramine, vilazodone, aripiprazole, sertraline in rats. A UPLC-MS/MS method was developed and validated for the simultaneous determination of clomipramine, vilazodone, aripiprazole, sertraline in rat plasma. using a mobile phase consisting of acetonitrile: 0.1% formic acid in water: 10 mM ammonium formate (10: 45: 45, v/v/v) pumped through Waters Sunfire-C18 column (5 µm, 4. 6× 50 mm), using escitalopram as internal standard. Detection was carried out using a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring mode. Ionization was conducted using electrospray ion source in positive ionization mode, the method was linear over the concentration range (1–400 ng/ml), with good results for coefficient of variation at LLOQ and QCs for all the cited drugs; confirming method precision and accuracy. This method was successfully applied to a drug- herb pharmacokinetic study in rats to assess the potential effect of consumption of khat on the bioavailability of clomipramine, vilazodone, aripiprazole, sertraline. It was found that khat consumption significantly increase the bioavailability of these drugs this might be due to inhibition of their metabolic enzymes CYP450, CYP2D6 and CYP3A4 isoforms, with the consequent increase in their systemic exposure and potential adverse effects. thus, a potentially significant herb-drug interaction must be considered in patients chewing khat while prescribing one of these drugs.