High-sensitivity liquid chromatography–tandem mass spectrometry method for the simultaneous determination of sodium picosulfate and its three major metabolites in human plasma
2013
Yang, Yong | Yu, Jinghua | Lu, Youming | Xia, Yu | Zhong, Dafang | Chen, Xiaoyan
Sodium picosulfate (PICO-Na) is a member of the polyphenolic group of stimulant laxatives. Its major metabolites in humans are its active aglycone BHPM (bis-(p-hydroxyphenyl)-pyridyl-2-methane), the monoglucuronide (M1) and the monosulfate (M2) of BHPM. A sensitive, specific and rapid liquid chromatography–tandem mass spectrometry method was established and validated for the simultaneous determination of picosulfate (PICO) and its three major metabolites in human plasma to investigate the pharmacokinetics of PICO and its major metabolites. Following protein precipitation with acetonitrile, chromatographic separation was achieved on a Luna 5u C18(2) column using gradient elution starting with 10% of 10mM ammonium acetate followed by increasing percentages of acetonitrile to eliminate interferences due to in-source conversion of the conjugated metabolites. Detection was performed on a tandem mass spectrometer equipped with an electrospray ionization source operated in the positive mode, using the transitions of m/z 438.1→m/z 278.1 for PICO, m/z 278.1→m/z 184.2 for BHPM, m/z 454.1→m/z 184.2 for M1, and m/z 358.1→m/z 184.2 summed with m/z 358.1→m/z 278.1 for M2. Deuterium labeled compounds of the analytes were used as the internal standard, two of which, M1-d12 and M2-d12, were synthesized in-house. The method was validated in concentration ranges of 0.150–40.0ng/mL for PICO and M2, 0.600–160ng/mL for BHPM, and 0.045–12.0ng/mL for M1 with acceptable accuracy and precision. The method was successfully applied to characterize the pharmacokinetic profiles of PICO and its metabolites in healthy volunteers after a single oral administration of 5mg PICO-Na.
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