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Quantitation of motexafin lutetium in human plasma by liquid chromatography-tandem mass spectrometry and inductively coupled plasma-atomic emission spectroscopy

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Abstract

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) methods were developed and validated for the evaluation of motexafin lutetium (MLu, lutetium texaphyrin, PCI-0123) pharmacokinetics in human plasma. The LC-MS/MS method was specific for MLu, whereas the ICP-AES method measured total elemental lutetium. Both methods were fast, simple, precise, and accurate. For the LC-MS/MS method, a closely related analogue (PCI-0353) was used as the internal standard (IS). MLu and the IS were extracted from plasma by protein precipitation and injected onto and LC-MS/MS system configured with a C18 column and an electrospray interface. The lower limit of quantitation was 0.05 μg MLu mL−1, with a signal-to-noise ratio of 15∶1. The response was linear from 0.05 to 5.0 μg MLu mL−1. For the ICP-AES method, indium was used as the IS. The sample was digested with nitric acid, diluted, filtered, and then injected onto the ICP-AES system. Two standard curve ranges were validated to meet the expected range of sample concentrations: 0.5 to 50, and 0.1 to 10 μg Lu mL−1. The LC-MS/MS and ICP-AES methods were validated to establish accuracy, precision, analyte stability, and assay robustness. Interday precision and accuracy of quality control samples were ≤6.3% coefficient of variation (CV) and within 2.2% relative error (RE) for the LC-MS/MS method, and ≤8.7% CV and within 4.9% RE for the ICP-AES method. Plasma samples from a subset of patients in a clinical study were analyzed using both methods. For a representative patient, over 90% of the elemental lutetium in plasma could be ascribed to intact MLu at early time points. This percentage decreased to 59% at 48 hours after dosing, suggesting that some degradation and/or metabolism of the drug may have occurred.

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Authors and Affiliations

  1. Pharmacyclics, Inc, 94085-4521, Sunnyvale, CA

    Dale Miles & Tarak D. Mody

  2. MDS Pharma Services, 621 Rose Street, 68501, Lincoln, NE

    Lori I. Hatcher, John Fiene, Mark Stiles, Patrick P. Lin & J. W. Lee

Authors
  1. Dale Miles
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  2. Tarak D. Mody
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  3. Lori I. Hatcher
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  4. John Fiene
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  5. Mark Stiles
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  6. Patrick P. Lin
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  7. J. W. Lee
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Correspondence to J. W. Lee.

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Published: August 12, 2003

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Miles, D., Mody, T.D., Hatcher, L.I. et al. Quantitation of motexafin lutetium in human plasma by liquid chromatography-tandem mass spectrometry and inductively coupled plasma-atomic emission spectroscopy. AAPS PharmSci 5, 23 (2003). https://doi.org/10.1208/ps050323

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  • DOI: https://doi.org/10.1208/ps050323

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