title: Monitoring of threo-methylphenidate enantiomers in oral fluid by capillary electrophoresis with head-column field-amplified sample injection.
abstract: Threo-methylphenidate is a chiral psychostimulant drug widely prescribed to treat attention-deficit hyperactivity disorder in children and adolescents. An enantioselective CE-based assay with head-column field-amplified sample stacking for analysis of threo-methylphenidate enantiomers in liquid/liquid extracts of oral fluid is described. Analytes are electrokinetically injected across a short water plug placed at the capillary inlet and become stacked at the interface between plug and buffer. Enantiomeric separation occurs within a few minutes in a pH 3.0 phosphate/triethanolamine buffer containing 20 mg/mL (2-hydroxypropyl)-β-CD as chiral selector. The assay with six point multilevel internal calibration provides a linear response for each enantiomer in the 10-200 ng/mL concentration range, is simple, inexpensive, and reproducible, and has an LOQ of 5 ng/mL. It was applied to oral fluid patient samples that were collected up to 12 h after intake of an immediate release tablet and two different extended release formulations with racemic methylphenidate. Drug profiles could thereby be assessed in a stereoselective way. Almost no levorotary threo-methylphenidate enantiomer was detected after intake of the two extended release formulations, whereas this enantiomer was detected during the first 2.5 h after intake of the immediate release preparation. The noninvasive collection of oral fluid is an attractive alternative to plasma for the monitoring of methylphenidate exposure in the pediatric community.
authors.affiliation: Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Regula
authors.initials: R
authors.lastname: Theurillat
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thormann
mesh_terms: D000293:Adolescent; D002648:Child; D016903:Drug Monitoring; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000032:analysis* / Q000737:chemistry*; D012463:Saliva / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D008774:Methylphenidate
keywords: Capillary electrophoresis; Ritalin; Therapeutic drug monitoring