title: Analysis of chlormequat in human urine as a biomarker of exposure using liquid chromatography triple quadrupole mass spectrometry.
abstract: In this study, a method using liquid chromatography triple quadrupole mass spectrometry (LC/MS/MS) is described for the analysis of the plant growth regulator chlormequat (CCC) in human urine. Analysis was carried out using selected reaction monitoring (SRM) in the positive ion mode. [(2)H(4)] labeled CCC as internal standard (IS) was used for quantification of CCC. The limit of detection (LOD) was determined to 0.1 ng/mL. The method was linear in the range 0.3-800 ng/mL urine and had a within-run precision of 4-9%. The between-run precision was determined at urine levels of 7.0 and 31 ng/mL and found to be 5 and 6% respectively. The reproducibility was 3-6%. To validate CCC as a biomarker of exposure, the method was applied in a human experimental oral exposure to CCC. Two healthy volunteers received 25 μg/kg b.w. CCC in a single oral dose followed by urine sampling for 46 h post-exposure. The CCC was estimated to follow a first order kinetic and a two compartment model with an elimination half-life of 2-3h and 10-14 h respectively. One hundred 24h urine samples were collected from non-occupationally exposed individuals in the general population in southern Sweden. All samples had detectable levels above the LOD 0.1 ng/mL urine. The median levels were 4 ng/mL of CCC in unadjusted urine. The levels found in the population samples are several magnitudes lower than those found in the experimental exposure, which corresponds to an oral exposure of 50% of the ADI for CCC.
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden. Christian.lindh@med.lu.se
authors.forename: Christian H
authors.initials: CH
authors.lastname: Lindh
authors.forename: Margareta
authors.initials: M
authors.lastname: Littorin
authors.forename: Gunvor
authors.initials: G
authors.lastname: Johannesson
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D002716:Chlormequat / Q000493:pharmacokinetics / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods*; D004781:Environmental Exposure / Q000032:analysis*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010937:Plant Growth Regulators / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D015415:Biomarkers; D010937:Plant Growth Regulators; D002716:Chlormequat