Clinical Chemistry Link to Randox Laboratories Web Site
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Clinical Chemistry 53: 1827-1834, 2007. First published August 16, 2007; 10.1373/clinchem.2007.090811
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow 090811.Supplemental Data
Right arrow All Versions of this Article:
clinchem.2007.090811v1
53/10/1827    most recent
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Annesley, T. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Annesley, T. M.
Related Collections
Right arrow General Clinical Chemistry
Right arrow Drug Monitoring and Toxicology
Right arrow Automation and Analytical Techniques
(Clinical Chemistry. 2007;53:1827-1834.)
© 2007 American Association for Clinical Chemistry, Inc.

Automation and Analytical Techniques

Methanol-Associated Matrix Effects in Electrospray Ionization Tandem Mass Spectrometry

Thomas M. Annesleya

Department of Pathology, University of Michigan Health Sciences Center, Ann Arbor, MI.

aAddress correspondence to the author at: University Hospital, Rm. 2G332, 1500 East Medical Center Dr., Ann Arbor, MI 48109-5054. Fax 734-763-4095; e-mail annesley{at}umich.edu.

Background: Matrix effects can profoundly reduce the performance of electrospray ionization mass spectrometry. Preliminary observations indicated that the methanol used in the mobile phase could be a source of differential ionization or ion suppression.

Methods: Drug stability studies, analysis of biological extracts, mixing experiments, and postcolumn infusions were used to test 9 commercial methanols for ionization differences in liquid chromatography-tandem mass spectrometry assays for immunosuppressants. Area responses for the drugs and internal standards were compared for mobile phases prepared with each selected methanol. Postcolumn infusion experiments were performed to confirm the degree of ionization differences occurring at the ion source, and to evaluate the proportions of ammonium, sodium, and potassium adducts.

Results: The decrease in signal for the immunosuppressant drugs was shown to result from differential ionization associated with the selected methanols. Product ion intensity varied by 10-fold among the methanols tested. For sirolimus, tacrolimus, and mycophenolic acid, the percentage change in ionization was the same for the drug and its corresponding internal standard. Postcolumn sirolimus infusion evaluation revealed that a 1000-fold analyte concentration difference did not affect ionization. The proportions of ammonium, sodium, and potassium adducts of sirolimus precursor ions differed in relation to the source of methanol.

Conclusions: Organic solvents used in mobile phases and extract preparation of biological samples may be associated with ion suppression, affecting adduct formation and assay sensitivity.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the American Association for Clinical Chemistry.