Methanol-associated matrix effects in electrospray ionization tandem mass spectrometry

被引:48
作者
Annesley, Thomas M. [1 ]
机构
[1] Univ Michigan, Hlth Sci Ctr, Dept Pathol, Ann Arbor, MI 48109 USA
关键词
D O I
10.1373/clinchem.2007.090811
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
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. (c) 2007 American Association for Clinical Chemistry
引用
收藏
页码:1827 / 1834
页数:8
相关论文
共 33 条
  • [1] Application of commercial calibrators for the analysis of immunosuppressant drugs in whole blood
    Annesley, TM
    [J]. CLINICAL CHEMISTRY, 2005, 51 (02) : 457 - 460
  • [2] Quantification of mycophenolic acid and glucuronide metabolite in human serum by HPLC-tandem mass spectrometry
    Annesley, TM
    Clayton, LT
    [J]. CLINICAL CHEMISTRY, 2005, 51 (05) : 872 - 877
  • [3] Simple extraction protocol for analysis of immunosuppressant drugs in whole blood
    Annesley, TM
    Clayton, L
    [J]. CLINICAL CHEMISTRY, 2004, 50 (10) : 1845 - 1848
  • [4] Ion suppression in mass spectrometry
    Annesley, TM
    [J]. CLINICAL CHEMISTRY, 2003, 49 (07) : 1041 - 1044
  • [5] Total plasma homocysteine measured by liquid chromatography-tandem mass spectrometry with use of 96-well plates
    Arndt, T
    Guessregen, B
    Hohl, A
    Heicke, B
    [J]. CLINICAL CHEMISTRY, 2004, 50 (04) : 755 - 757
  • [6] Quantification of free mycophenolic acid and its glucuronide metabolite in human plasma by liquid-chromatography using mass spectrometric and ultraviolet absorbance detection
    Atcheson, B
    Taylor, PJ
    Mudge, DW
    Johnson, DW
    Pillans, PI
    Tett, SE
    [J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2004, 799 (01): : 157 - 163
  • [7] Bonfiglio R, 1999, RAPID COMMUN MASS SP, V13, P1175, DOI 10.1002/(SICI)1097-0231(19990630)13:12<1175::AID-RCM639>3.0.CO
  • [8] 2-0
  • [9] Quantification by liquid chromatography tandem mass spectrometry of mycophenolic acid and its phenol and acyl glucuronide metabolites
    Brandhorst, Gunnar
    Streit, Frank
    Goetze, Sandra
    Oellerich, Michael
    Armstrong, Victor William
    [J]. CLINICAL CHEMISTRY, 2006, 52 (10) : 1962 - 1964
  • [10] Quantitative analysis of s-adenosylmethionine and s-adenosylhomocysteine in neurulation-stage mouse embryos by liquid chromatography tandem mass spectrometry
    Burren, Katie A.
    Mills, Kevin
    Copp, Andrew J.
    Greene, Nicholas D. E.
    [J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2006, 844 (01): : 112 - 118