Simultaneous Determination of Four Related Substances in Olmesartan Medoxomil Hydrochlorothiazide Tablets by HPLC-Principal Component Self-Control with Correct Factor
- VernacularTitle:HPLC-加校正因子的主成分自身对照法同时测定奥美沙坦酯氢氯噻嗪片中4种有关物质含量
- Author:
Haoxian LI
1
,
2
;
Huaqing LIN
1
;
Junjian LI
2
;
Yuanjian WANG
2
;
Rong LIU
2
;
Chuqin YU
1
Author Information
1. College of Pharmacy，Guangdong Pharmaceutical University/Guangdong Provincial Key Laboratory of Advanced Drug Delivery，Guangzhou 510006，China
2. Guanghzou Bostal Drug Delivery Co.，Ltd.，Guanghzou 510530，China
- Publication Type:Journal Article
- Keywords:
Olmesartan medoxomil hydrochlorothiazide tablets;
Related substances;
HPLC;
Principal component self-control
- From:
China Pharmacy
2020;31(7):825-830
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To establish the method for simultaneous determination of four known related substances （olmesartan，olmesartan ester dimer ，olmesartan ester alkene ，benzothiadiazine impurity ，called impurity A ，B，C，D for short ）in Olmesartan medoxomil hydrochlorothiazide tablets. METHODS ：HPLC-principal component self-control with correction factor were adopted. The determination was performed on YMC-Triart C 8 column with mobile phase A consisted of acetonitrile- 0.015 mol/L potassium dihydrogen phosphate solution （pH adjusted to 2.8 with phosphoric acid ）（70 ∶ 30，V/V），mobile phase B consisted of acetonitrile-0.015 mol/L potassium dihydrogen phosphate solution （pH adjusted to 2.8 with phosphoric acid ）（15 ∶ 85，V/V）at the flow rate of 0.8 mL/min（gradient elution ）. The detection wavelength was set at 265 nm，and column temperature was 25 ℃. The temperature of injector was 4 ℃；the injection volume was 10 μL. RESULTS：The correction factors of impurity A ，B，C，D were 1.42，1.17，0.89，0.92，respectively. The linear range of olmesartan medoxomil ，hydrochlorothiazide and impurity A ，B，C，D were 0.252 7-7.580 0，1.152 1-4.562 9，0.244 0-18.299 0，0.244 7-3.670 8，0.265 2-3.978 3 and 0.149 9-4.497 3 μg/mL（r≥ 0.999 7），respectively. The limits of detection were 0.084 2，0.050 7，0.081 3，0.081 6，0.088 4，0.050 0 μg/mL，respectively. The quantitative limits were 0.252 7，0.152 1，0.244 0，0.244 7，0.265 2 and 0.149 9 μg/mL，respectively. The results of intermediate precision ，stability（24 h）and repeatability tests all met the relevant requirements. The average recovery rates were 104.00％-108.04％，102.00％-104.94％，100.99％-106.89％，92.00％-95.18％，102.00％-105.06％，103.90％-107.00％（n＝3）， respectively. The contents of impurity A ，B and D in 3 batches of Olmesartan medoxomil hydrochlorothiazide tablets were 0.90％ -1.00％ ，0-0.11％ ，0.16％ -0.24％ ，respectively. The impurity C and other impurities were not detected. There is no significant difference between the results measured by the established method and by the external standard method. CONCLUSIONS：The method has been proved to be highly sensitive and reproducible. It can be used to simultaneously determine four known substances in Olmesartan medoxomil hydrochlorothiazide tablets.
