Measurement of free drug and clinical end-point by high-performance liquid chromatography-mass spectrometry: Applications and implications for pharmacokinetic and pharmacodynamic studies

Atcheson, B., Taylor, P. J., Pillans, P. I. and Tett, S. E. (2003) Measurement of free drug and clinical end-point by high-performance liquid chromatography-mass spectrometry: Applications and implications for pharmacokinetic and pharmacodynamic studies. Analytica Chimica Acta, 492 2003: 157-169. doi:10.1016/S0003-2670(03)00359-3


Author Atcheson, B.
Taylor, P. J.
Pillans, P. I.
Tett, S. E.
Title Measurement of free drug and clinical end-point by high-performance liquid chromatography-mass spectrometry: Applications and implications for pharmacokinetic and pharmacodynamic studies
Journal name Analytica Chimica Acta   Check publisher's open access policy
ISSN 0003-2670
Publication date 2003
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/S0003-2670(03)00359-3
Volume 492
Issue 2003
Start page 157
End page 169
Total pages 13
Editor L. Guydens
R. P. Baldwin
Place of publication Netherlands
Publisher Elsevier BV
Collection year 2003
Language eng
Subject C1
320503 Clinical Pharmacology and Therapeutics
730199 Clinical health not specific to particular organs, diseases and conditions
Abstract Free drug measurement and pharmacodymanic markers provide the opportunity for a better understanding of drug efficacy and toxicity. High-performance liquid chromatography (HPLC)-mass spectrometry (MS) is a powerful analytical technique that could facilitate the measurement of free drug and these markers. Currently, there are very few published methods for the determination of free drug concentrations by HPLC-MS. The development of atmospheric pressure ionisation sources, together with on-line microdialysis or on-line equilibrium dialysis and column switching techniques have reduced sample run times and increased assay efficiency. The availability of such methods will aid in drug development and the clinical use of certain drugs, including anti-convulsants, anti-arrhythmics, immunosuppressants, local anaesthetics, anti-fungals and protease inhibitors. The history of free drug measurement and an overview of the current HPLC-MS applications for these drugs are discussed. Immunosuppressant drugs are used as an example for the application of HPLC-MS in the measurement of drug pharmacodynamics. Potential biomarkers of immunosuppression that could be measured by HPLC-MS include purine nucleoside/nucleotides, drug-protein complexes and phosphorylated peptides. At the proteomic level, two-dimensional gel electrophoresis combined with matrix-assisted laser desorption/ionisation time-of-flight (TOF) MS is a powerful tool for identifying proteins involved in the response to inflammatory mediators. (C) 2003 Elsevier Science B.V. All rights reserved.
Keyword Free Drug
Pharmacodynamics
Immunosuppressants
Hplc-mass Spectrometry
Protein-binding
Acid-induced Immunosuppression
Renal-transplant Recipients
Immunophilin-binding Assay
Free Mycophenolic-acid
Human-serum-albumin
Human-plasma
Valproic Acid
In-vivo
Chemistry, Analytical
Inosine 5'-monophosphate Dehydrogenase
Q-Index Code C1

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
2004 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 02:07:40 EST