| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received on July 8, 2003
Accepted on October 13, 2003
Drug Monitoring and Toxicology |
1 Department of Clinical Chemistry, George-August University Gottingen, D-37075 Gottingen, Germany
2 Central Institute for Clinical Chemistry and Laboratory Medicine, Klinikum Stuttgart, Stuttgart, Germany
* To whom correspondence should be addressed. E-mail: varmstro{at}med.uni-goettingen.de.
Background: Because mycophenolic acid (MPA) is highly protein bound and because the free fraction is the pharmacologically active portion, a rapid, reliable, and sensitive procedure is required to study the relationship between free MPA and treatment efficacy/toxicity. Liquid chromatography-tandem mass spectrometry is ideally suited for such a method.
Methods: Free MPA was isolated from plasma by ultrafiltration. An online extraction cartridge with a column-switching technique, analytical liquid chromatography over an Aqua Perfect C$1 column, and electrospray tandem mass spectrometry was used to quantify free and total MPA. To investigate ion suppression, a continuous infusion of MPA was introduced into the effluent from the HPLC column, and different ultrafiltrates and extracted plasma samples were injected on the column.
Results: A chromatographic run time of 4 min separated MPA from metabolites and internal standard, thereby avoiding interference from in-source fragmentation. Ion suppression occurred well before elution of MPA and internal standard. The lower limit of quantification for free MPA was 0.5 µg/L, and the method was linear to 1000 µg/L. Interassay imprecision (CV) was <10% for free MPA (0.5-333 µg/L). Agreement was good for free MPA (n = 52) and total MPA (n = 106) between the propose method and a validated HPLC method with ultraviolet detection. The Passing-Bablok regression line was: y = 0.95x + 0.27 µg/L for free MPA and y = 0.98x + 0.03 µg/L for total MPA.
Conclusions: The presented method allows the accurate, precise, and rapid determination of free and total MPA in plasma over a wide analytical range covering the concentrations relevant to pharmacokinetic studies and routine monitoring of this drug.© 2004 American Association for Clinical Chemistry
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  J. Kuhn, C. Prante, S. Schon, C. Gotting, and K. Kleesiek Measurement of Fibrosis Marker Xylosyltransferase I Activity by HPLC Electrospray Ionization Tandem Mass Spectrometry Clin. Chem., December 1, 2006; 52(12): 2243 - 2249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Brandhorst, F. Streit, S. Goetze, M. Oellerich, and V. W. Armstrong Quantification by Liquid Chromatography Tandem Mass Spectrometry of Mycophenolic Acid and Its Phenol and Acyl Glucuronide Metabolites Clin. Chem., October 1, 2006; 52(10): 1962 - 1964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Cussonneau, M. Bolon-Larger, and R. Boulieu Adsorption of Mycophenolic Acid and Its Phenolic Glucuronide to Glass, Polystyrene, and Polypropylene Containers. Clin. Chem., May 1, 2006; 52(5): 904 - 906. [Full Text] [PDF]
|
|
|
|
|
|
T. M. Annesley and L. T. Clayton Quantification of Mycophenolic Acid and Glucuronide Metabolite in Human Serum by HPLC-Tandem Mass Spectrometry Clin. Chem., May 1, 2005; 51(5): 872 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Anderson Candidate-based proteomics in the search for biomarkers of cardiovascular disease J. Physiol., February 15, 2005; 563(1): 23 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kinter Toward Broader Inclusion of Liquid Chromatography-Mass Spectrometry in the Clinical Laboratory Clin. Chem., September 1, 2004; 50(9): 1500 - 1502. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
