Qualitative and quantitative analysis of related substances in clotrimazole cream
10.16438/j.0513-4870.2018-0545
- VernacularTitle:克霉唑乳膏中有关物质的定性与定量分析
- Author:
Xiao-mei YANG
1
;
Yong-kun LIANG
2
;
Liang-zhong YU
2
;
Wen-ling YANG
1
;
Hai-bo MA
1
;
Jing-qing MU
1
;
Rui-xun WANG
1
;
Qing LI
1
;
Ran LIU
1
;
Kai-shun BI
1
Author Information
1. Shenyang Pharmaceutical University, Shenyang 110016, China
2. Guangdong China Resources Shunfeng Pharmaceutical Co. Ltd., Foshan 528300, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
clotrimazole cream;
HPLC;
related substances;
structure identification
- From:
Acta Pharmaceutica Sinica
2018;53(12):2093-2098
- CountryChina
- Language:Chinese
-
Abstract:
For qualitative and quantitative analysis of related substances in clotrimazole cream, HPLC-Q-TOF spectrometer was used to analyze the fragmentation pathways and identify structures of the related substances. Five related substances named by BP (2018) were identified as impurity A ((2-chlorophenyl)-diphenylmethanol), impurity B (para-clotrimazole isomer), impurity E (2-chlorobenzophenone), impurity F (1-tritylimidazole) and impurity 4 (9-(2-chlorophenyl)-fluorene), respectively, by using impurity references matching and comparison with the literature data. Four related substances were detected in clotrimazole cream except impurity E, and 9-(2-chlorophenyl)-fluorene is the first identified impurity in this preparation. To establish an HPLC method for determination of the related substances in Clotrimazole Cream, the Agilent Poroshell Bonuns RP column was used (100 mm×4.6 mm, 2.7 μm) with UV detection at 215 nm. The mobile phase was acetonitrile-10 mmol·L-1 dipotassium phosphate buffer (adjusted with phosphoric acid to pH of 5.80) with a flow rate of 1.0 mL·min-1. Gradient elution was used. The column temperature was maintained at 40℃. A good linear behavior was achieved between component's concentrations and peak area for impurity A, B, E, F within the range of 0.20-10.02 μg·mL-1, 0.20-10.00 μg·mL-1, 0.20-10.10 μg·mL-1, 0.10-5.01 μg·mL-1 with the correlation coefficients were 0.999 7, 1.000 0, 1.000 0, 0.999 9, respectively. The average recoveries were 94.3%, 95.0%, 100.0%, 99.6% with RSDs were 2.8%, 2.2%, 1.1%, 2.7%, respectively (n=9). LOQ were 200.4, 200.0, 202.0, 100.2 ng·mL-1, respectively. LOD were 57.25, 57.14, 57.71, 28.63 ng·mL-1, respectively. The developed method was simple, rapid, accurate and effective for testing related substances in clotrimazole cream to control its quality, ensuring the safety of clinical medication.
