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Determination of naltrexone and 6β-naltrexol in human blood: comparison of high-performance liquid chromatography with spectrophotometric and tandem-mass-spectrometric detection

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Abstract

We present data for a comparison of a liquid-chromatographic method coupled with tandem mass spectrometry (LC-MS/MS) and a high-performance liquid-chromatographic method with column switching and UV spectrophotometric detection. The two methods were developed for determination of naltrexone and 6β-naltrexol in blood serum or plasma aiming to be used for therapeutic drug monitoring to guide the treatment of patients with naltrexone. For the high-performance liquid chromatography (HPLC)/UV detection, online sample cleanup was conducted on Perfect Bond C18 material with 2% (vol/vol) acetonitrile in deionized water. Drugs were separated on a C18 column using 11.5% (vol/vol) acetonitrile and 0.4% (vol/vol) N,N,N,N-tetramethylethylenediamine within 20 min. LC-MS/MS used naltrexone-d 3 and 6β-naltrexol-d 4 as internal standards. After protein precipitation, the chromatographic separation was performed on a C18 column by applying a methanol gradient (5–100%, vol/vol) with 0.1% formic acid over 9.5 min. The HPLC/UV method was found to be linear for concentrations ranging from 2 to 100 ng/ml, with a regression correlation coefficient of r 2 > 0.998 for naltrexone and 6β-naltrexol. The limit of quantification was 2 ng/ml for naltrexone and 6β-naltrexol. For the LC-MS/MS method the calibration curves were linear (r² > 0.999) from 0.5 to 200 ng/ml for both substances, and the limit of quantification was 0.5 ng/ml. The concentrations measured by the two methods correlated significantly for both substances (r² > 0.967; p < 0.001). Both methods could be used for therapeutic drug monitoring. The HPLC/UV method was advantageous regarding automatization and costs, whereas LC-MS/MS was superior with regard to sensitivity.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Mainz, Untere Zahlbacherstraße 8, 55131, Mainz, Germany

    Sonja Brünen, Susann Finger, Felix Korf & Christoph Hiemke

  2. Institute of Clinical Chemistry and Laboratory Medicine, University of Mainz, 55131, Mainz, Germany

    Ralf Krüger & Karl J. Lackner

  3. Central Institute for Mental Health, University of Heidelberg, 68159, Mannheim, Germany

    Falk Kiefer

  4. Department of Psychiatry and Psychotherapy, University of Hamburg, 20146, Hamburg, Germany

    Klaus Wiedemann

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  1. Sonja Brünen
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  2. Ralf Krüger
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Correspondence to Christoph Hiemke.

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Brünen, S., Krüger, R., Finger, S. et al. Determination of naltrexone and 6β-naltrexol in human blood: comparison of high-performance liquid chromatography with spectrophotometric and tandem-mass-spectrometric detection. Anal Bioanal Chem 396, 1249–1257 (2010). https://doi.org/10.1007/s00216-009-3301-z

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  • DOI: https://doi.org/10.1007/s00216-009-3301-z

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