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In vitro Metabolism Analysis of Sulfamerazine in Mice Liver by Ultra Performance Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry

[ Vol. 14 , Issue. 1 ]

Author(s):

Zhe Meng, Zhihong Shi, Ming Su* and Hanwen Sun*   Pages 17 - 22 ( 6 )

Abstract:


Background: Sulfonamide antibiotics are the second most frequent cause of allergic drug reactions (after the β-lactams). Activity and side effects of sulfonamide may be attributed to their metabolites. To the best of our knowledge there is no in vitro metabolism study for sulfamerazine (SMR) available in the literature. The main objectives of this research are to develop an analytic method for screening, identifying and quantifying SMR and its active metabolites and for in vitro metabolism study.

Methods: An ultra performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometric (UPLC-QTOF-MS) method was used for establishing the accurate mass databases of SMR and N-ASMR as well as non-target analytes and for in vitro screening, identification, and quantification of SMR and its metabolites N4-acetylsulfamerazine (N-ASMR) in mice liver homogenates.

Result: The limit of detection (LOD) and limit of quantification (LOQ) were 1.0 and 5.0 µg L-1 for SMR and 12.0 and 20 µgL-1 for N4-acetylsulfamerazine (N-ASMR), respectively. Peak area intra-day RSD (n=6) and inter-day RSD (n=9) were 5.0 and 8.2 % for SMR, and 4.3 and 7.2% for N-ASMR, respectively. The identification of targeted analytes (SMR and N-ASMR) was conducted based on the established accurate mass database (both retention time and accurate mass). SMR could be metabolized via acetylating by acetoacetyl coenzyme A, and two isomers of ASMR were confirmed. Methylation of SMR was found, and four isomers of a metabolite of SMR were confirmed.

Conclusion: The developed UPLC-QTOF-MS method is rapid and effective for screening, identification, and quantification of SMR and its metabolites. The metabolism mechanism and accurate mass databases for target and non-target metabolites of SMR in mice liver are valuable for metabolism study, with high accurate mass.

Keywords:

Sulfamerazine, ultra performance liquid chromatography, quadrupole time-of-flight mass spectrometry, mice liver, in vitro metabolism.

Affiliation:

College of Chemistry and Environmental Science, Hebei University, Key Laboratory of Analytical Science and Technology of Hebei Province, Baoding 071002, College of Chemistry and Environmental Science, Hebei University, Key Laboratory of Analytical Science and Technology of Hebei Province, Baoding 071002, College of Chemistry and Environmental Science, Hebei University, Key Laboratory of Analytical Science and Technology of Hebei Province, Baoding 071002, College of Chemistry and Environmental Science, Hebei University, Key Laboratory of Analytical Science and Technology of Hebei Province, Baoding 071002

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