Determination of Drugs in Plasma Samples by High-Performance Liquid Chromatography–Tandem Mass Spectrometry for Therapeutic Drug Monitoring of Schizophrenic Patients

Abstract

This work describes the development of a simple, sensitive and selective method based on high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) to determine antipsychotics (olanzapine, quetiapine, clozapine, haloperidol and chlorpromazine) along with antidepressants (mirtazapine, paroxetine, citalopram, sertraline, imipramine, clomipramine and fluoxetine), anticonvulsants (carbamazepine and lamotrigine) and anxiolytics (diazepam and clonazepam) in plasma samples obtained from schizophrenic patients. The samples were prepared by protein precipitation. The target drugs were separated on an XSelect SCH C18 column (100 mm × 2.1 mm × 2.5 µm) within 8.0 min by means of gradient elution. The drugs were then detected on a quadrupole tandem mass spectrometer equipped with an electrospray ionization source, operating in the multiple reactions monitoring mode and in the positive ionization mode. The LC-MS-MS method was linear range from subtherapeutic to toxic concentrations with lower limit of quantification values ranged from 0.2 to 5.0 ng mL(-1), precision with coefficient of variation values lower than 12%, and accuracy ranged from 90 to 108%. The developed method enabled successful analysis of the target drugs in plasma samples obtained from 51 schizophrenic patients. Therapeutic drug monitoring revealed that many of the evaluated schizophrenic patients presented altered plasma concentrations of the analyzed drugs. These altered concentrations resulted from pharmacokinetic interactions among the medications prescribed to treat schizophrenia.

Isotopically labelled paroxetine standard allows for definite structure elucidation of the paroxetine tandem mass spectrum

“…The antidepressant paroxetine, which is pharmacologically used to treat various neurological diseases worldwide (e.g. depression, panic, anxiety, posttraumatic stress), 1 4 The deuterated positions of this internal standard are not described in the text, but in this case, all six deuterium atoms obviously remained at the product ion, which further confirms our observation.…”

“…Domingues et al dealt with the determination of drugs for therapeutic drug monitoring of schizophrenic patients. They also used m / z 70 as the characteristic product ion for paroxetine, and they even included paroxetine‐ d 6 as internal standard and determined m / z 76 as product ion . The deuterated positions of this internal standard are not described in the text, but in this case, all six deuterium atoms obviously remained at the product ion, which further confirms our observation.…”

A fast and simple approach for the quantification of 40 illicit drugs, medicines, and pesticides in blood and urine samples by UHPLC‐MS/MS

“…Several articles have been published using different work‐up procedures designed for the detection of different analytes of interest, and a wide variety of substances can be detected in blood or also in urine in a single analysis . In some cases, there is no previous knowledge about the poisoning history of the patient.…”

“…Therefore, the analytical strategy in toxicological analysis should focus on developing features such as simultaneous monitoring of a large number of toxic agents, simplicity, and rapid sample preparation . In the last years, ultra‐high performance liquid chromatography‐tandem mass spectrometry (UHPLC‐MS/MS) has proven to be a very useful analytical tool that provides a satisfactory identification and quantitation of substances in the emergency toxicology field . In addition, some classical techniques have been reported for multi‐analyte approach aiming the quantitation of drugs and poisons in biosamples.…”

“…[6][7][8][9][10][11] Several articles have been published using different work-up procedures designed for the detection of different analytes of interest, and a wide variety of substances can be detected in blood or also in urine in a single analysis. [12][13][14][15][16][17][18] In some cases, there is no previous knowledge about the poisoning history of the patient. Then the preliminary screening procedures are necessary for the identification of the possible substance(s) involved.…”