HPLC测定赛利司他有关物质及降解产物

Determination of the Related Substances of Cetilistat by HPLC

关键词:  赛利司他  高效液相色谱法  有关物质

Key words:  cetilistat  HPLC  related substances

摘要:

目的 建立HPLC测定赛利司他有关物质的方法。方法 采用Agilent Phenyl色谱柱（250 mm×4.6 mm，5 μm），以5 mmol·L^-1磷酸二氢钾（用10%磷酸调pH值至4.0）-乙腈为流动相进行梯度洗脱，流速为1.0 mL·min^-1，检测波长为226 nm。结果 各杂质与主峰之间的分离度良好。开环杂质（杂质A）、2-十七烷基氧-6-甲基-4氢-3，1-苯并噁嗪-4-酮（杂质B）、2-十八烷基氧-6-甲基-4氢-3，1-苯并噁嗪-4-酮（杂质C）浓度分别在0.049 5~1.981 μg·mL^-1，0.059 9~0.399 1 μg·mL^-1，0.059 6~0.397 5 μg·mL^-1内与峰面积呈良好的线性关系，r均为0.999 9；杂质A、B、C加样回收率的平均值分别为104.2%，107.0%和107.8%，RSD分别为2.09%，1.77%和2.18%。结论 本方法简便、准确可靠，适用于赛利司他中有关物质的控制。

Abstract:

OBJECTIVE To establish an HPLC method for determining the contents of the related substances of cetilistat. METHODS The condition of detection were as follows:Agilent Phenyl column (250 mm×4.6 mm, 5 μm), the gradient mobile phase consisted of 5 mmol·L^-1 potassium dihydrogen phosphate (adjust with 10% phosphoric acid to pH 4.0) and acetonitrile with a flow rate of 1.0 mL·min^-1, the UV detection wavelength was 226 nm. RESULTS The resolution of cetilistat and relate substances was good. The calibration curves were linear in the range of 0.049 5-1.981 0 μg·mL^-1 for impurity A (r=0.999 9); the calibration curves were linear in the range of 0.059 9-0.399 1 μg·mL^-1 for impurity B (r=0.999 9); the calibration curves were linear in the range of 0.059 6-0.397 5 μg·mL^-1 for impurity C (r=0.999 9). The average recoveries of impurity A, impurity B and impurity C were 104.2%, 107.0% and 107.8% respectively; the RSDs were 2.09%, 1.77% and 2.18%, respectively. CONCLUSION The method is simple, accurate, reliable and can be used for the quality control of the related substances of cetilistat.