Quantitation of motexafin lutetium in human plasma by liquid chromatography-tandem mass spectrometry and inductively coupled plasma-atomic emission spectroscopy
Journal Title: The AAPS Journal - Year 2003, Vol 5, Issue 3
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.
Authors and Affiliations
Dale Miles, Tarak D. Mody, Lori I. Hatcher, John Fiene, Mark Stiles, Patrick P. Lin, J. W. Lee
Keywords
Related Articles
- EP ID EP681969
- DOI 10.1208/ps050323
- Views 98
- Downloads 0
Virtual coupling of pyran protons in the 1H NMR spectra of C- and N-glucoronides: Dependence on substitution and solvent
We have observed that certain C-and N-glucuronides prepared as intermediates for breast cancer preventives demonstrate non-first order 1H NMR spectra that are not the result of impurities or degradation but are instead d...
Structure–Activity Relationships of Tariquidar Analogs as Multidrug Resistance Modulators
The review summarizes the most recent achievements in structure–activity relationship (SAR) studies of tariquidar and its analogs. Tariquidar is one of the most promising representatives of the third generation o...
Analyzing Subvisible Particles in Protein Drug Products: a Comparison of Dynamic Light Scattering (DLS) and Resonant Mass Measurement (RMM)
Aggregation is common in protein drug manufacture, and while the effects of protein particulates are under investigation, many techniques applicable for their characterization have been recently developed. Among the meth...
Mechanism-Based Pharmacokinetic Modeling to Evaluate Transporter-Enzyme Interplay in Drug Interactions and Pharmacogenetics of Glyburide
The purpose of this study is to characterize the involvement of hepato-biliary transport and cytochrome-P450 (CYP)-mediated metabolism in the disposition of glyburide and predict its pharmacokinetic variability due to dr...
Repeat Analysis and Incurred Sample Reanalysis: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team
The A7 harmonization team (A7 HT), a part of the Global Bioanalysis Consortium (GBC), focused on reviewing best practices for repeat analysis and incurred sample reanalysis (ISR) as applied during regulated bioanalysis....