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Determination of imatinib and its active metabolite N-desmethyl imatinib in human plasma by liquid chromatography/tandem mass spectrometry

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Abstract

Imatinib is a first-line treatment for chronic myelogenous leukaemia (CML). The pharmacokinetics of imatinib in patients with CML are characterised by large interpatient variability. Concentration monitoring of imatinib and its active metabolite N-desmethyl imatinib (DMI) is considered necessary to enhance the safe and effective use of imatinib. A rapid, simple and sensitive liquid chromatography/tandem mass spectrometry assay was developed for the simultaneous determination of imatinib and its metabolite DMI in human plasma. After proteins were precipitated with acetonitrile, imatinib, DMI and the internal standard D8-imatinib were resolved on a Gemini-NX 3 μm C18 column using gradient elution of 0.05 % formic acid and methanol. The three compounds were detected using electrospray ionisation in the positive mode. Standard curves of imatinib and DMI were adequately fitted by quadratic equations (r > 0.999) over the concentration range of 10 to 2,000 ng/mL which encompasses clinical concentrations. Bias was ≤±8.3 %, intra- and inter-day coefficients of variation (imprecision) were ≤8.0 % and the limit of quantification was 10 ng/mL for both imatinib and DMI. The assay is being used successfully in clinical practice to enhance the safe and effective use of imatinib.

Representative LC-MS/MS chromatogram of imatinib, N–desmethyl imatinib and the internal standard D8-imatinib in human plasma

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Authors and Affiliations

  1. Clinical Pharmacology, Department of Medicine, University of Otago—Christchurch, PO Box 4345, 2 Riccarton Avenue Christchurch Central, Christchurch, 8011, New Zealand

    Mei Zhang, Murray L. Barclay & Evan J Begg

  2. Toxicology, Canterbury Health Laboratories, Hagley Avenue, Addington, Christchurch, 8011, New Zealand

    Grant A. Moore

  3. Department of Haematology, University of Otago—Christchurch, 2 Riccarton Avenue Christchurch Central, Christchurch, 8011, New Zealand

    Liam J. Fernyhough

Authors
  1. Mei Zhang
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  2. Grant A. Moore
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  3. Liam J. Fernyhough
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  4. Murray L. Barclay
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  5. Evan J Begg
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Correspondence to Mei Zhang.

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Zhang, M., Moore, G.A., Fernyhough, L.J. et al. Determination of imatinib and its active metabolite N-desmethyl imatinib in human plasma by liquid chromatography/tandem mass spectrometry. Anal Bioanal Chem 404, 2091–2096 (2012). https://doi.org/10.1007/s00216-012-6284-0

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  • DOI: https://doi.org/10.1007/s00216-012-6284-0

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