Determination of Tricyclohexylphosphine in the Intermediate of Ticagrelor with Derivatization Pretreatment by UPLC-ESI-MS/MS
Substances containing phosphine have potential genotoxicity and can directly cause DNA damage at trace levels,leading to cancer and posing a threat to human health.Therefore,strict control of such impurities in drugs is necessary.In this study,a method was established for the detection of tricyclohexylphosphine in ticagrelor.Tricyclohexylphosphine was derivatized into tricyclohexyloxophosphine after reaction with hydrogen peroxide.An Agilent Poroshell 120 EC-C18 chromatographic column(100 mm×4.6 mm,2.7 μm)was used.The mobile phase was 0.1％formic acid-0.1％formic acid methanol(5∶95),the flow rate was 0.5 mL/min,and the column temperature was 30 ℃.Electrospray ionization source(ESI)positive ion scanning was used to collect quantitative ion pairs 297.2→83 for the detection of tricyclohexyloxophosphine in the multi-reaction monitoring mode(MRM).Tricyclohexylphosphine exhibited a good linear relationship with peak area in the concentration range of 1.45～28.90 ng/mL(r=0.999 8).The limit of quantitation was 0.14 ng/mL,and the limit of detection was 0.072 ng/mL.The average sample recovery rate was 99.5％,and the RSD was 5.4％(n=9).This method could be used for the detection of tricyclohexylphosphine in Ticagrelor by simple pretreatment to derive tricyclohexyloxophosphine,which was more stable,specific,sensitive,accurate,and short in analysis time,which was expected to improve the clinical safety of the drug Ticagrelor.
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