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Quantitative determination of phenothiazine derivatives in human plasma using monolithic silica solid-phase extraction tips and gas chromatography-mass spectrometry.

Abstract

Solid-phase extraction (SPE) using micropipette tips is a useful technique to prepare samples prior to mass spectrometry. However, most commercial SPE tips have loading capacities that are insufficient for quantitative determination. In this paper, we describe a rapid method for quantitative microanalysis of five phenothiazine derivatives, chlorpromazine, levomepromazine, promazine, promethazine and trimeprazine, using a recently introduced C(18) monolithic silica SPE tip, the MonoTip C(18), for extraction from human plasma. The drugs could be extracted within 5 min from 0.1-mL plasma samples, eluted with methanol, and the eluate injected directly into a gas chromatograph prior to mass spectrometry analysis. Only 0.7 mL of solvent was required for each step of the extraction process. The recoveries of the five phenothiazines spiked into plasma were 91-95% and the limits of quantification for each drug were between 0.25 and 2.0 ng/0.1 mL. The maximum intra- and inter-day coefficient of variation was 11%. The validated method was successfully used to quantify the plasma concentration of levemepromazine in a human subject after oral administration of the drug. This new method is expected to have wide applications as a pretreatment for the rapid, quantitative determination of drug concentrations in plasma samples.

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  • Authors

    Kumazawa T, Hasegawa C, Uchigasaki S, Lee XP, Suzuki O, Sato K

    Institution

    Department of Legal Medicine, Showa University School of Medicine, Tokyo, Japan. kumazawa@med.showa-u.ac.jp

    Source

    Journal of chromatography. A 1218:18 2011 May 6 pg 2521-7

    MeSH

    Adult
    Drug Stability
    Female
    Gas Chromatography-Mass Spectrometry
    Humans
    Linear Models
    Methotrimeprazine
    Phenothiazines
    Porosity
    Reproducibility of Results
    Sensitivity and Specificity
    Silicon Dioxide
    Solid Phase Extraction

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21429493