Abstract
For the first time, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) multi-analyte approach based on a simple liquid–liquid extraction was developed and validated for fast target screening and quantification of benzodiazepines and Z-drugs in case of driving ability and crime responsibility in the three most important biosamples whole blood, plasma, and serum. Whole blood, plasma, and serum (500 μL each) were extracted twice at pH 7.4 and at pH 10 with ether/ethyl acetate (1:1). Separation, detection, and quantification were performed using LC-MS/MS with electrospray ionization in positive mode. The method was validated with respect to selectivity, ion suppression/enhancement of co-eluting analytes, matrix effects, recovery, process efficiency, accuracy and precision, stabilities, and limits of detection and quantification. For accuracy and precision, full calibration was performed with ranges from subtherapeutic to toxic concentrations. The presented LC-MS/MS approach as part of a universal multi-analyte concept for over 100 drugs was applicable for selective detection as well as accurate and precise quantification in whole blood, plasma, and serum. The approach was selective, sensitive, accurate, and precise for 16 of the 19 tested drugs in whole blood, 18 in plasma, and 17 in serum. Only semiquantitative results could be obtained for zopiclone because of its instability in all tested biosamples.
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References
Schweizerisches Zentrum für Qualitätskontrolle (2010) Serum oder plasma. www.cscq.ch/SiteCSCQ/FichierPDF_DE/serum_oder_plasma.pdf
Remane D, Meyer MR, Wissenbach DK, Maurer HH (2011) Anal Bioanal Chem 400:2093–2107
Remane D, Meyer MR, Wissenbach DK, Maurer HH (2011) Anal Bioanal Chem 401:1352
Maurer HH (2005) Clin Biochem 38:310–318
Kratzsch C, Tenberken O, Peters FT, Weber AA, Kraemer T, Maurer HH (2004) J Mass Spectrom 39:856–872
Saar E, Gerostamoulos D, Drummer OH, Beyer J (2010) J Mass Spectrom 45:915–925
Laloup M, Ramirez Fernandez MM, de Boeck G, Wood M, Maes V, Samyn N (2005) J Anal Toxicol 29:616–626
Ambach L, Hernández Redondo A, König S, and Weinmann W. (2013) Drug Test Anal. Jul 19. doi:10.1002/dta.1505.
Gonzalez O, Alonso RM, Ferreirós N, Weinmann W, Zimmermann R, Dresen S (2011) J Chromatogr B Anal Technol Biomed Life Sci 879:243–252
van Laar MW, Volkerts ER (1998) CNS Drugs 10:383–396
Steentoft A, Linnet K (2009) Forensic Sci Int 184:74–79
Steentoft A, Worm K (1993) Forensic Sci Int 33:45–48
Kratzsch C, Tenberken O, Peters FT, Weber AA, Kraemer T, Maurer HH (2004) J Mass Spectrom 39:856–872
Nakamura M (2011) Biomed Chromatogr 25:1283–1307
Laloup M, Ramirez Fernandez MM, de Boeck G, Wood M, Maes V, Samyn N (2005) J Anal Toxicol 29:616–626
Rust KY, Wilkens H, Kaiser R, Bregel D, Wilske J, Kraemer T (2012) Ther Drug Monit 34:729–735
Maurer HH, Pfleger K, Weber AA (2011) Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites. Wiley-VCH, Weinheim
Maurer HH, Kratzsch C, Kraemer T, Peters FT, Weber AA (2002) J Chromatogr B Anal Technol Biomed Life Sci 773:63–73
Matuszewski BK, Constanzer ML, Chavez-Eng CM (2012) Anal Chem 75:3019–3030
Peters FT, Paul LD, Musshoff F, Aebi B, Auwaerter V, Kraemer T, Skopp G (2009) Toxichem Krimtech 76:185–208
Shah VP, Midha KK, Findlay JW, Hill HM, Hulse JD, McGilveray IJ, McKay G, Miller KJ, Patnaik RN, Powell ML, Tonelli A, Viswanathan CT, Yacobi A (2000) Pharm Res 17:1551–1557
Peters FT, Drummer OH, Musshoff F (2007) Forensic Sci Int 165:216–224
Peters FT (2006) Method validation using LC-MS. In: Applications of liquid chromatography-mass spectrometry in toxicology. Pharmaceutical Press, London
Schulz M, Iwersen-Bergmann S, Andresen H, and Schmoldt A (2012) Crit Care 16:R136, http://ccforum.com/content/16/4/R136
TIAFT blood level list (2013) http://www.gtfch.org/cms/images/stories/Updated_TIAFT_list_202005.pdf
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The authors would like to thank Dr. Andrea E. Steuer for the helpful discussion.
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Montenarh, D., Hopf, M., Maurer, H.H. et al. Detection and quantification of benzodiazepines and Z-drugs in human whole blood, plasma, and serum samples as part of a comprehensive multi-analyte LC-MS/MS approach. Anal Bioanal Chem 406, 803–818 (2014). https://doi.org/10.1007/s00216-013-7513-x
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DOI: https://doi.org/10.1007/s00216-013-7513-x