Development of a liquid chromatography tandem mass spectrometry method for mycophenolic acid in plasma and saliva : application to study the pharmacokinetics of mycophenolic acid in Hong Kong Chinese renal transplant patients

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Development of a liquid chromatography tandem mass spectrometry method for mycophenolic acid in plasma and saliva : application to study the pharmacokinetics of mycophenolic acid in Hong Kong Chinese renal transplant patients

 

Author: Fok, Ho-tong
Title: Development of a liquid chromatography tandem mass spectrometry method for mycophenolic acid in plasma and saliva : application to study the pharmacokinetics of mycophenolic acid in Hong Kong Chinese renal transplant patients
Degree: M.Sc.
Year: 2011
Subject: Hong Kong Polytechnic University -- Dissertations
Phenolic acids -- Pharmacokinetics
Kidneys -- Transplantation
Department: Dept. of Health Technology and Informatics
Pages: xi, 97 leaves : ill. ; 30 cm.
InnoPac Record: http://library.polyu.edu.hk/record=b2426754
URI: http://theses.lib.polyu.edu.hk/handle/200/6024
Abstract: The aim of this project was to develop a simple, sensitive and specific liquid chromatography tandem mass spectrometry method (LC-MS/MS) to quantitate mycophenolic acid (MPA) in plasma and saliva. This method was used to study the correlations between plasma total MPA, plasma free MPA and saliva MPA. Correlation study results were then used to investigate if saliva can be used in place of plasma total and free MPA measurement for therapeutic monitoring of MPA. Also, this method was used for the pharmacokinetic study of MPA in Hong Kong Chinese renal transplant patients. Development of a LC-MS/MS method for plasma total and free MPA, and saliva MPA measurement was successful. To separate MPA from MPA glucuronide (MPAG) and other sample matrix interferences, a gradient elution was performed on a Thermo Hypersil-Gold C18 column (50 mm X 2.1 mm, 3 μm particle size), with mobile phase A contained 2mM ammonium acetate, 0.1% (v/v) formic acid and deionised water, and mobile phase B contained 2mM ammonium acetate, 0.1% (v/v) formic acid and absolute methanol, at a flow rate of 0.6 ml/min. Signal monitoring was performed by the multiple reaction monitoring (MRM) mode using transaction m/z 320.6 → 207.1 for MPA; m/z 323.6 → 210.1 for deuterium labeled internal standard (MPA-d3) and m/z 513.6 → 207.1 for MPAG. MPA and MPA-d3 were eluted in 3.5 min and the injection-to-injection time was 7.5 min. Analytical performance of the developed method was satisfactory. For plasma total MPA measurement, the linearity range was 0.1-100 mg/L. For plasma free MPA and saliva MPA measurement, the linearity ranges were 5-500 μg/L. The correlation coefficients were 0.999 (plasma total MPA vs. plasma free MPA), 0.946 (plasma total MPA vs. saliva MPA), and 0.944 (plasma free MPA vs. saliva MPA) in three renal transplant patients. Results showed good correlation as reported by other studies. Therefore, saliva may be used as an alternative to plasma total and free MPA monitoring for renal transplant patients. In conclusion, the developed LC-MS/MS method for MPA will support a new clinical service of TDM for transplant patients of MPA.

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