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The quantitative analysis of heroin, methadone and their metabolites and the simultaneous detection of cocaine, acetylcodeine and their metabolites in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry.
J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Sep 25; 824(1-2):213-21.JC

Abstract

For a pharmacokinetic-pharmacodynamic study in opioid tolerant patients, who were treated with heroin in combination with methadone, a liquid chromatographic assay with tandem mass spectrometry detection (LC-MS/MS) was developed for the simultaneous determination of heroin, methadone, heroin metabolites 6-monoacetylmorphine, morphine, and morphine-6 and 3-glucuronide and methadone metabolite EMDP. To detect any abuse of substances besides the prescribed opioids the assay was extended with the detection of cocaine, its metabolites benzoylecgonine and norcocaine and illicit heroin adulterants acetylcodeine and codeine. Heroin-d6, morphine-d3, morphine-3-glucuronide-d3 and methadone-d9 were used as internal standards. The sample pre-treatment consisted of solid phase extraction using mixed mode sorbent columns (MCX Oasis). Chromatographic separation was performed at 25 degrees C on a reversed phase Zorbax column with a gradient mobile phase consisting of ammonium formate (pH 4.0) and acetonitrile. The run time was 15 min. MS with relatively mild electrospray ionisation under atmospheric pressure was applied. The triple quadrupole MS was operating in the positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over a concentration range of 5-500 ng/mL for all analytes. The total recovery of heroin varied between 86 and 96% and of the heroin metabolites between 76 and 101%. Intra-assay and inter-assay accuracy and precision of all analytes were always within the designated limits (< or =20% at lower limit of quantification (LLQ) and < or =15% for other samples). This specific and sensitive assay was successfully applied in pharmacokinetic studies with medically prescribed heroin and toxicological cases.

Authors+Show Affiliations

Slotervaart Hospital, Department of Pharmacy and Pharmacology, Louwesweg 6, P.O. Box 90440, 1006 BK Amsterdam, The Netherlands. ej.rook@cbg-meb.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16103023

Citation

Rook, Elisabeth J., et al. "The Quantitative Analysis of Heroin, Methadone and Their Metabolites and the Simultaneous Detection of Cocaine, Acetylcodeine and Their Metabolites in Human Plasma By High-performance Liquid Chromatography Coupled With Tandem Mass Spectrometry." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 824, no. 1-2, 2005, pp. 213-21.
Rook EJ, Hillebrand MJ, Rosing H, et al. The quantitative analysis of heroin, methadone and their metabolites and the simultaneous detection of cocaine, acetylcodeine and their metabolites in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;824(1-2):213-21.
Rook, E. J., Hillebrand, M. J., Rosing, H., van Ree, J. M., & Beijnen, J. H. (2005). The quantitative analysis of heroin, methadone and their metabolites and the simultaneous detection of cocaine, acetylcodeine and their metabolites in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 824(1-2), 213-21.
Rook EJ, et al. The Quantitative Analysis of Heroin, Methadone and Their Metabolites and the Simultaneous Detection of Cocaine, Acetylcodeine and Their Metabolites in Human Plasma By High-performance Liquid Chromatography Coupled With Tandem Mass Spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Sep 25;824(1-2):213-21. PubMed PMID: 16103023.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The quantitative analysis of heroin, methadone and their metabolites and the simultaneous detection of cocaine, acetylcodeine and their metabolites in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry. AU - Rook,Elisabeth J, AU - Hillebrand,Michel J X, AU - Rosing,Hilde, AU - van Ree,Jan M, AU - Beijnen,Jos H, PY - 2003/09/18/received PY - 2005/04/11/revised PY - 2005/05/25/accepted PY - 2005/8/17/pubmed PY - 2005/10/20/medline PY - 2005/8/17/entrez SP - 213 EP - 21 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J Chromatogr B Analyt Technol Biomed Life Sci VL - 824 IS - 1-2 N2 - For a pharmacokinetic-pharmacodynamic study in opioid tolerant patients, who were treated with heroin in combination with methadone, a liquid chromatographic assay with tandem mass spectrometry detection (LC-MS/MS) was developed for the simultaneous determination of heroin, methadone, heroin metabolites 6-monoacetylmorphine, morphine, and morphine-6 and 3-glucuronide and methadone metabolite EMDP. To detect any abuse of substances besides the prescribed opioids the assay was extended with the detection of cocaine, its metabolites benzoylecgonine and norcocaine and illicit heroin adulterants acetylcodeine and codeine. Heroin-d6, morphine-d3, morphine-3-glucuronide-d3 and methadone-d9 were used as internal standards. The sample pre-treatment consisted of solid phase extraction using mixed mode sorbent columns (MCX Oasis). Chromatographic separation was performed at 25 degrees C on a reversed phase Zorbax column with a gradient mobile phase consisting of ammonium formate (pH 4.0) and acetonitrile. The run time was 15 min. MS with relatively mild electrospray ionisation under atmospheric pressure was applied. The triple quadrupole MS was operating in the positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over a concentration range of 5-500 ng/mL for all analytes. The total recovery of heroin varied between 86 and 96% and of the heroin metabolites between 76 and 101%. Intra-assay and inter-assay accuracy and precision of all analytes were always within the designated limits (< or =20% at lower limit of quantification (LLQ) and < or =15% for other samples). This specific and sensitive assay was successfully applied in pharmacokinetic studies with medically prescribed heroin and toxicological cases. SN - 1570-0232 UR - https://www.unboundmedicine.com/medline/citation/16103023/The_quantitative_analysis_of_heroin_methadone_and_their_metabolites_and_the_simultaneous_detection_of_cocaine_acetylcodeine_and_their_metabolites_in_human_plasma_by_high_performance_liquid_chromatography_coupled_with_tandem_mass_spectrometry_ DB - PRIME DP - Unbound Medicine ER -