Action and use
Antihelminthic.
DEFINITION
Fenbendazole Oral Suspension is an aqueous suspension of Fenbendazole.
The oral suspension complies with the requirements stated under Oral Liquids and with the following requirements.
Content of fenbendazole, C15H13N3O2S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is the same as that of the principal peak in the chromatogram obtained with solution (2).
TESTS
Related impurities A, B and 1
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Mix with the aid of ultrasound, a quantity of the oral suspension containing 0.1 g of Fenbendazole with 50 mL of 0.1M methanolic hydrochloric acid for 30 minutes, cool, dilute to 100 mL with methanol (65%), mix and filter through a glass- fibre filter (Whatman GF/C is suitable).
(2) Dilute 1 volume of a 0.001% w/v solution of fenbendazole impurity A EPCRS (methyl (1H-benzimidazol-2-yl)carbamate) in 0.1M methanolic hydrochloric acid to 2 volumes with methanol (65%).
(3) Dilute 1 volume of a 0.001% w/v solution of fenbendazole impurity B EPCRS (methyl(5-chloro-1H-benzimidazol-2- yl)carbamate) in 0.1M methanolic hydrochloric acid to 2 volumes with methanol (65%).
(4) Dilute 1 volume of a 0.001% w/v solution of fenbendazole impurity 1 BPCRS ((5-phenylthio)-2-aminobenzimidazole) in 0.1M methanolic hydrochloric acid to 2 volumes with methanol (65%).
(5) Dilute 1 volume of a solution containing 0.002% w/v each of fenbendazole impurity A EPCRS, fenbendazole impurity B EPCRS, fenbendazole impurity 1 BPCRS and 0.20% w/v of fenbendazole BPCRS in 0.1M methanolic hydrochloric acid to 2 volumes with methanol (65%).
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 280 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
350 volumes of a 0.5% w/v solution of sodium dihydrogen orthophosphate and 650 volumes of methanol containing 1.88 g of sodium hexanesulfonate, the pH of which has been adjusted to 3.5 with orthophosphoric acid.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (5) closely resembles the reference chromatogram supplied with fenbendazole BPCRS.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to fenbendazole impurity A (methyl (1H-benzimidazol-2-yl)carbamate) is not greater than the area of the corresponding peak in the chromatogram obtained with solution (2), (0.5%);
the area of any peak corresponding to fenbendazole impurity B (methyl(5-chloro-1H-benzimidazol-2-yl)carbamate) is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.5%);
the area of any peak corresponding to fenbendazole impurity 1 ((5-phenylthio)-2-aminobenzimidazole) is not greater than the area of the corresponding peak in the chromatogram obtained with solution (4) (0.5%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Mix with the aid of ultrasound a quantity of the oral suspension containing 0.1 g of Fenbendazole with 50 mL of 0.1M methanolic hydrochloric acid for 30 minutes, cool, dilute to 100 mL with methanol (65%), mix and filter through a glass- fibre filter (Whatman GF/C is suitable). Dilute 5 volumes of the resulting solution to 50 volumes with 0.1M hydrochloric acid in methanol (85%).
(2) 0.01% w/v of fenbendazole BPCRS in a mixture of 1 volume of 0.1M hydrochloric acid and 1 volume of methanol (85%).
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (5) closely resembles the reference chromatogram supplied with fenbendazole BPCRS.
DETERMINATION OF CONTENT
Calculate the content of C15H13N3O2S in the oral suspension from the chromatogram obtained and using the declared content of C15H13N3O2S in fenbendazole BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A and B listed under Fenbendazole and the following:
1. (5-phenylthio)-2-aminobenzimidazole.
