TY - JOUR
T1 - LC–MS/MS method for quantitation of mycophenolic acid, mycophenolic acid acyl-glucuronide, and 7-O-mycophenolic acid glucuronide in serum
AU - Merrigan, Stephen D.
AU - Kish-Trier, Erik
AU - Seegmiller, Jesse C.
AU - Johnson-Davis, Kamisha L.
N1 - Publisher Copyright:
© 2017
PY - 2017/1
Y1 - 2017/1
N2 - Mycophenolic acid (MPA) is the active metabolite of the immunosuppressant drug mycophenolate mofetil (MMF), which is commonly prescribed after organ transplantation in conjunction with other immunosuppressants. MMF therapy is monitored to balance therapeutic efficacy with minimizing adverse effects associated with high serum concentrations. A LC–MS/MS method was developed for the quantification of MPA and two additional metabolites, 7-O-mycophenolic acid glucuronide (MPAG) and mycophenolic acid acyl-glucuronide (AcMPAG), in serum using reverse-phase chromatography and multiple reaction monitoring (MRM) in positive electrospray ionization mode. Analytes were chromatographically resolved and the method was linear from 0.5 to 30.0 µg/ml MPA, 4.7 to 300 µg/ml MPAG, and from 0.5 to 30.0 µg/ml AcMPAG. Calibration curves for all analytes had r ≥ 0.990. Intra- and inter-assay imprecision coefficients of variation (CVs) were ≤6.9% and ≤14.5%, respectively. No ion suppression or interferences were observed. The method compared favorably with an unaffiliated reference laboratory. Retrospective data analyses indicate interpatient differences in drug metabolism.
AB - Mycophenolic acid (MPA) is the active metabolite of the immunosuppressant drug mycophenolate mofetil (MMF), which is commonly prescribed after organ transplantation in conjunction with other immunosuppressants. MMF therapy is monitored to balance therapeutic efficacy with minimizing adverse effects associated with high serum concentrations. A LC–MS/MS method was developed for the quantification of MPA and two additional metabolites, 7-O-mycophenolic acid glucuronide (MPAG) and mycophenolic acid acyl-glucuronide (AcMPAG), in serum using reverse-phase chromatography and multiple reaction monitoring (MRM) in positive electrospray ionization mode. Analytes were chromatographically resolved and the method was linear from 0.5 to 30.0 µg/ml MPA, 4.7 to 300 µg/ml MPAG, and from 0.5 to 30.0 µg/ml AcMPAG. Calibration curves for all analytes had r ≥ 0.990. Intra- and inter-assay imprecision coefficients of variation (CVs) were ≤6.9% and ≤14.5%, respectively. No ion suppression or interferences were observed. The method compared favorably with an unaffiliated reference laboratory. Retrospective data analyses indicate interpatient differences in drug metabolism.
KW - 7-O-mycophenolic acid glucuronide
KW - Immunosuppressant
KW - Liquid chromatography
KW - Mass spectrometry
KW - Mycophenolate mofetil
KW - Mycophenolic acid
KW - Mycophenolic acid acyl-glucuronide
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U2 - 10.1016/j.clinms.2017.07.001
DO - 10.1016/j.clinms.2017.07.001
M3 - Article
AN - SCOPUS:85050647025
SN - 2376-9998
VL - 3
SP - 41
EP - 48
JO - Clinical Mass Spectrometry
JF - Clinical Mass Spectrometry
ER -