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

Author(s)

Domingues, Diego Soares ^[1] ; Lemos Pinto, Monia Aparecida ^[2] ; de Souza, Israel Donizeti ^[1] ; Cecilio Hallak, Jaime Eduardo ^[3] ; de Souza Crippa, Jose Alexandre ^[3] ; Costa Queiroz, Maria Eugenia ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Quim, Fac Filosofia Ciencias & Letras Ribeirao Preto, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF ANALYTICAL TOXICOLOGY; v. 40, n. 1, p. 28-36, JAN-FEB 2016.
• Web of Science Citations: 11

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 C-18 column (100 mm x 2.1 mm x 2.5 A mu m) 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. (AU)

• FAPESP's process: 12/10705-9 - Development of selective phases for in-tube SPME/LC-MS/MS analysis of parabens and drugs in biological samples
• Grantee: Maria Eugênia Queiroz Nassur
• Support Opportunities: Regular Research Grants