title: Determination of levamisole, aminorex, and pemoline in plasma by means of liquid chromatography-mass spectrometry and application to a pharmacokinetic study of levamisole.
abstract: Levamisole is an anti-helminthic drug and gained forensic interest after it was found that it was used as a cocaine adulterant. A liquid chromatography-mass spectrometry (LC-MS) method for the determination of levamisole and its metabolite aminorex in human plasma is described. Selectivity is given; calibration curves were linear within a calibration range of 1 ng/mL-500 ng/mL. Limits of detection and quantification (LODs, LOQs) were 0.85 ng/mL for levamisole and 0.09 ng/mL, and 0.34 ng/mL for aminorex, respectively. Precision data was in accordance with the GTFCh guidelines. The validated method was successfully applied to study the pharmacokinetics of levamisole after administration of 100 mg of levamisole orally. Levamisole could be detected up to 36 h after ingestion in serum, while aminorex never exceeded the LOQ. A one-compartment model best described levamisole pharmacokinetics. The following parameters were calculated: ka = 1.2 [1/h], CL/F = 52 l/h, V/F = 347 l, f (renal) = 0.0005, t ½ = 2.0 h, AUC = 1923 ng/mL*h, cmax = 214 ng/mL, tmax = 1.98 h. Levamisole could be quantified in 42.5% of cocaine--positive plasma samples (2.2 to 224 ng/mL). Aminorex was positive in only 11.3% of the cases; however, it was never found higher than the LOQ. Pemoline, another stimulant detected in horse urine samples after administration of levamisole, was not found either in serum or in urine of this pharmacokinetic study. In post-mortem cases, levamisole and aminorex could be detected in femoral blood and the urine of cocaine users. Pemoline was not detected.
authors.affiliation: Institute of Forensic Medicine, University of Bonn, Stiftsplatz 12, D-53111, Bonn, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Hess
authors.forename: Natalie
authors.initials: N
authors.lastname: Ritke
authors.forename: Konrad
authors.initials: K
authors.lastname: Sydow
authors.forename: Lena-Maria
authors.initials: LM
authors.lastname: Mehling
authors.forename: Hauke
authors.initials: H
authors.lastname: Ruehs
authors.forename: Burkhard
authors.initials: B
authors.lastname: Madea
authors.forename: Frank
authors.initials: F
authors.lastname: Musshoff
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000635:Aminorex / Q000032:analysis* / Q000378:metabolism; D000871:Anthelmintics / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D006207:Half-Life; D006801:Humans; D007978:Levamisole / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D057230:Limit of Detection; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008954:Models, Biological; D010389:Pemoline / Q000032:analysis
chemical_list: D000871:Anthelmintics; D007978:Levamisole; D000635:Aminorex; D010389:Pemoline
keywords: LC-MS/MS; aminorex; cocaine adulterants; levamisole; pemoline; pharmacokinetics