Simultaneous Quantification of Antipsychotic and Antiepileptic Drugs and Their Metabolites in Human Saliva Using UHPLC-DAD

Molecules. 2019 Aug 14;24(16):2953. doi: 10.3390/molecules24162953.

Abstract

Neuroleptics and antiepileptics are excreted in saliva, which can, therefore, be very useful in determining their concentration in the body. This study presents a method developed to simultaneously identify five neuroleptics-olanzapine, quetiapine, risperidone, aripiprazole, and clozapine-and the antiepileptic carbamazepine together with their metabolites: N-demethyl olanzapine, norquetiapine, 9-OH-risperidone, dehydroaripiprazole, N-desmethylclozapine, and carbamazepine-10,11 epoxide. Chlordiazepoxide was used as the internal standard. Strata-X-C columns were used for isolation of the compounds. Chromatographic analysis was carried out using UHPLC with a diode array detector (DAD). A mixture of acetonitrile and water with the addition of formic acid and 0.1% triethylamine was used as the mobile phase. The developed method was validated by determining the linearity for all analytes in the range 10-1000 ng/mL and the value of R2 > 0.99. Intra- and inter-day precision were also determined, and the relative standard deviation (RSD) value in both cases did not exceed 15%. To determine the usefulness of the developed method, saliva samples were collected from 40 people of both sexes treated with the tested active substances both in monotherapy and in polypragmasy. In all cases, the active substances tested were identified.

Keywords: UHPLC-DAD; carbamazepine; metabolites; neuroleptics; saliva; simultaneous quantification.

MeSH terms

  • Anticonvulsants / chemistry
  • Anticonvulsants / pharmacology*
  • Antipsychotic Agents / chemistry
  • Antipsychotic Agents / pharmacokinetics*
  • Chromatography, High Pressure Liquid* / methods
  • Chromatography, High Pressure Liquid* / standards
  • Drug Stability
  • Humans
  • Molecular Structure
  • Reproducibility of Results
  • Saliva / metabolism*

Substances

  • Anticonvulsants
  • Antipsychotic Agents