Climbazol – Bestimmung von Dihydroxyclimbazol und Carboxyhydroxyclimbazol in Urin mittels UPLC-MS/MS
Biomonitoring-Methode
Katja Küpper1 (Methodenentwicklung)Christoph Schmidtkunz1 (Methodenentwicklung)
Isabell Schönrath1 (Methodenentwicklung)
Wolfgang Gries1 (Methodenentwicklung)
Gabriele Leng1 (Methodenentwicklung)
Gerhard Scherer2 (Methodenprüfung)
Max Scherer2 (Methodenprüfung)
Kirsten Riedel2 (Methodenprüfung)
Thomas Göen3 (Leitung der Arbeitsgruppe „Analysen in biologischem Material“ der Ständigen Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Deutsche Forschungsgemeinschaft)
Andrea Hartwig4 (Vorsitz der Ständigen Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Deutsche Forschungsgemeinschaft)
MAK Commission5
1 Currenta GmbH & Co. OHG, CUR-SIT-ABG-GS-BLM – Institut für Biomonitoring, Chempark Gebäude Q18, 51368 Leverkusen, Deutschland
2 ABF Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstraße 5, 82152 Planegg, Deutschland
3 Friedrich-Alexander-Universität Erlangen-Nürnberg, Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin, Henkestraße 9–11, 91054 Erlangen, Deutschland
4 Institut für Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut für Technologie (KIT), Adenauerring 20a, Geb. 50.41, 76131 Karlsruhe, Deutschland
5 Ständige Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Deutsche Forschungsgemeinschaft, Kennedyallee 40, 53175 Bonn, Deutschland
Abstract
The working group “Analyses in Biological Materials” of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) developed and verified this analytical method for the determination of two important urinary metabolites of climbazole – dihydroxyclimbazole ((OH)2-climbazole) and carboxyhydroxyclimbazole (cx-OH-climbazole). For the quantitation of the analytes, enzymatic hydrolysis of the urine sample is followed by online SPE‑UPLC‑MS/MS. The two diastereomers of (OH)2-climbazole are resolved chromatographically, and thus quantified separately. On the other hand, the diastereomers of cx-OH-climbazole coelute in one single peak. Calibration is performed using calibration standards prepared in pooled urine and processed analogously to the samples to be analysed. (OH)2‑climbazole-D6 and cx‑OH‑climbazole-D6 are applied as internal standards. The method provides reliable and accurate analytical results, as shown by the good precision data with standard deviations no greater than 9.2%. Good accuracy data were obtained with a mean relative recovery in the range of 96.9–102%. The method is both selective and sensitive, and provides a quantitation limit of 0.5 μg/l for (OH)2‑climbazole (per diastereomer) and cx‑OH‑climbazole (sum of diastereomers), respectively. The method enables the determination of occupational and environmental exposure to climbazole.
