Analysis of degradation pathways and impurities of losartan potassium
Objective To explore the degradation pathway of losartan potassium active pharmaceutical ingredient(API)through forced degradation test.Methods A high performance liquid chromatographic(HPLC)method was devel-oped for the determination of losartan potassium and its related substances on a Waters XBridge BEH C18(4.6 mm × 250 mm,5 μm)column with a mobile phase of 0.05％aqueous phosphoric acid solution-acetonitrile,gradient elution,flow rate of 1.0 mL·min-1,column temperature set at 30 ℃,detection wavelength 210 nm.The content of the main peak in the degra-dation solution of losartan potassium was determined to explore the degradation rate of losartan potassium API under the conditions of oxidation,acid hydrolysis,alkaline hydrolysis,thermal and photolysis.Results Among the 67 degradation con-ditions designed for this experiment,losartan potassium API was sensitive to oxidation(heating and room temperature),high temperature accompanied with high humidity,acidic condition environment,while in solution state it was sensitive to high temperature and light conditions.The molecular structures of four degradation impurities of losartan potassium were deter-mined,and their mass spectrum cleavage reaction mechanisms were clarified.Conclusion This experiment was conducted to simulate the degradation process of losartan potassium with a variety of environments involved in forced degradation.The study helps to explore the changes in impurities in drug storage and drug formulation production for quality control of losar-tan potassium API and its formulations.
Losartan potassiumOxidative destroyingAcid destroyingAlkali destroyingHigh temperature destroyingLight destroyingDegradation impurities
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