TY - JOUR
T1 - Validated LC-MS/MS method for the determination of maackiain and its sulfate and glucuronide in blood
T2 - Application to pharmacokinetic and disposition studies
AU - Gao, Song
AU - Yang, Zhen
AU - Yin, Taijun
AU - You, Ming
AU - Hu, Ming
N1 - Funding Information:
The work was supported by NIH AT003203 to MH at University of Houston (Houston, TX) and to MY at Medical College of Wisconsin (Milwaukee, WI).
PY - 2011/5/15
Y1 - 2011/5/15
N2 - The purpose of this study was to develop a simultaneous, sensitive and reproducible UPLC-MS/MS method to quantify maackiain and its phase II metabolites, maackiain-sulfate (M-7-S) and maackiain-glucuronide (M-7-G). A Waters BEH C18 column was used with acetonitrile/water as mobile phases. Analysis was performed under negative ionization electrospray mass spectrometer via the multiple reaction monitoring (MRM). The one-step protein precipitation by methanol was used to extract the analytes from plasma. The results showed that the linear response range was 5000-9.75nM for maackiain, M-7-S, and M-7-G. The lower limit of detection (LLOD) was 4.88nM for these three analytes. The intra-day variance is less than 12.4% and accuracy is in 85.7-102.0%. The inter-day variance is less than 11.2% and accuracy is in 89.6-122.2%. The analysis was done within 4.0min. Only 20μl of blood is needed for the analysis due to the high sensitivity of this method. The validated method was used for pharmacokinetic study in A/J mouse, maackiain Caco-2 cell culture model experiment, and maackiain glucuronidation/sulfation metabolism studies. The applications revealed that this method can be used for maackiain, M-7-S, and M-7-G analysis in both bioequivalent buffer and in blood.
AB - The purpose of this study was to develop a simultaneous, sensitive and reproducible UPLC-MS/MS method to quantify maackiain and its phase II metabolites, maackiain-sulfate (M-7-S) and maackiain-glucuronide (M-7-G). A Waters BEH C18 column was used with acetonitrile/water as mobile phases. Analysis was performed under negative ionization electrospray mass spectrometer via the multiple reaction monitoring (MRM). The one-step protein precipitation by methanol was used to extract the analytes from plasma. The results showed that the linear response range was 5000-9.75nM for maackiain, M-7-S, and M-7-G. The lower limit of detection (LLOD) was 4.88nM for these three analytes. The intra-day variance is less than 12.4% and accuracy is in 85.7-102.0%. The inter-day variance is less than 11.2% and accuracy is in 89.6-122.2%. The analysis was done within 4.0min. Only 20μl of blood is needed for the analysis due to the high sensitivity of this method. The validated method was used for pharmacokinetic study in A/J mouse, maackiain Caco-2 cell culture model experiment, and maackiain glucuronidation/sulfation metabolism studies. The applications revealed that this method can be used for maackiain, M-7-S, and M-7-G analysis in both bioequivalent buffer and in blood.
KW - Maackiain
KW - Maackiain-7-glucuronide
KW - Maackiain-7-sulfate
KW - Pharmacokinetics
KW - UPLC-MS/MS
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U2 - 10.1016/j.jpba.2011.01.015
DO - 10.1016/j.jpba.2011.01.015
M3 - Article
C2 - 21349678
AN - SCOPUS:79952249980
SN - 0731-7085
VL - 55
SP - 288
EP - 293
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
IS - 2
ER -