Determination of related genotoxic impurities in olmesartan medoxomil by HPLC-MS

LUAN Baolei; XU Xinjun; LIANG Guiting; YOU Mengmeng; LIU Guozhu

doi:10.11665/j.issn.1000-5048.20190308

Journal of China Pharmaceutical University > 2019 > 50(3): 325-329. > DOI: 10.11665/j.issn.1000-5048.20190308

LUAN Baolei, XU Xinjun, LIANG Guiting, YOU Mengmeng, LIU Guozhu. Determination of related genotoxic impurities in olmesartan medoxomil by HPLC-MS[J]. Journal of China Pharmaceutical University, 2019, 50(3): 325-329. DOI: 10.11665/j.issn.1000-5048.20190308

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Determination of related genotoxic impurities in olmesartan medoxomil by HPLC-MS

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The aim of this study was to establish a high performance liquid chromatography-mass spectrometry method for the determination of 5-(4′-(bromomethyl)-［1, 1′-biphenyl］-2-yl)- 1H-tetrazole(BBT1)and 5-(4′-(dibromomethyl)-［1, 1′-biphenyl］-2-yl)-1H-tetrazole(BBT2), which are two genotoxic impurities in olmesartan medoxomil. Chromatographic separation was based on an Agilent Zorbax Eclipse Plus C₁₈(250 mm × 4. 6 mm, 5 μm)column using water(containing 0. 1% formic acid)- acetonitrile as mobile phase in gradient elution mode. Mass spectrometry was operated in positive ion mode. Selective ion monitors were set at m/z 315 for BBT1 and at m/z 395 for BBT2. Good linear correlations were observed in the range of 0. 009 4- 0. 561 0 μg/mL(r=0. 998)with the quantification limit at 9. 35 ng/mL and the detection limit at 3. 12 ng/mL for BBT1, and in the range of 0. 018 2- 0. 547 5 μg/mL(r=0. 999)with the quantification limit at 18. 25 ng/mL and the detection limit at 6. 08 ng/mL for BBT2. Furthermore, the average recoveries of the three spiked concentration level were 96. 5%(n=9, RSD=4. 8%)and 98. 0%(n=9, RSD=5. 1%)for BBT1 and BBT2, respectively. The proposed method is simple, specific and accurate, and quite suitable for the determination of BBT1 and BBT2 in olmesartan medoxomil.

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