Fenbendazole
(fen ben' da zole).
Click to View Image
C15H13N3O2S 299.35

Carbamic acid, [5-(phenylthio)-lH-benzimidazol-2-yl]-, methyl ester.
Methyl 5-(phenylthio)-2-benzimidazolecarbamate [43210-67-9].
» Fenbendazole contains not less than 98.0 percent and not more than 101.0 percent of C15H13N3O2S, calculated on the dried basis.
Packaging and storage— Preserve in well-closed, light-resistant containers, and store at 25, excursions permitted between 15 and 30.
Labeling— Label it to indicate that it is for veterinary use only.
USP Reference standards 11
USP Fenbendazole RS Click to View Structure
USP Fenbendazole Related Compound A RS Click to View Structure
Methyl (1H-benzimidazole-2-yl)carbamate.
    C9H9N3O2    191.19
USP Fenbendazole Related Compound B RS Click to View Structure
Methyl [5(6)-chlorobenzimidazole-2-yl]carbamate.
    C9H8ClN3O2    225.63
USP Mebendazole RS Click to View Structure
Identification, Infrared Absorption 197K.
Loss on drying 731 Dry it at 100 to 105 for 3 hours: it loses not more than 1.0% of its weight.
Residue on ignition 281: not more than 0.3%.
Heavy metals, Method II 231: not more than 10 µg per g.
Related compounds—
Solution A— Prepare a mixture of water, methanol, and acetic acid (70:30:1).
Solution B— Prepare a mixture of methanol, water, and acetic acid (70:30:1).
Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system.
Hydrochloric methanol— Prepare a mixture of methanol and hydrochloric acid (99:1).
Standard solution 1— Dissolve an accurately weighed quantity of USP Fenbendazole RS in Hydrochloric methanol to obtain a solution having a known concentration of about 5 mg per mL. Dilute 1.0 mL of this solution with methanol to 200.0 mL. Dilute 5.0 mL of this solution with Hydrochloric methanol to 10.0 mL. This solution contains about 0.0125 mg of USP Fenbendazole RS per mL.
Standard solution 2— Dissolve an accurately weighed quantity of USP Fenbendazole Related Compound A RS in methanol to obtain a solution having a known concentration of about 0.1 mg per mL. Dilute 1.0 mL of this solution with Hydrochloric methanol to 10.0 mL, and mix.
Standard solution 3— Dissolve an accurately weighed quantity of USP Fenbendazole Related Compound B RS in methanol to obtain a solution having a known concentration of about 0.1 mg per mL. Dilute 1.0 mL of this solution with Hydrochloric methanol to 10.0 mL, and mix.
Resolution solution— Dissolve 10.0 mg of USP Fenbendazole RS and 10.0 mg of USP Mebendazole RS in 100.0 mL of methanol. Dilute 1.0 mL of this solution with Hydrochloric methanol to 10.0 mL, and mix.
Test solution— Dissolve 50.0 mg of Fenbendazole in 10.0 mL of Hydrochloric methanol.
Chromatographic system (see Chromatography 621 The liquid chromatograph is equipped with a 280-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows.
Time
(minutes)
Solution A
(%)
Solution B
(%)
Elution
0 100 0 equilibration
0–10 100®0 0®100 linear gradient
10–40 0 100 isocratic
40–50 0®100 100®0 linear gradient
Chromatograph the Resolution solution, and record the peak area responses as directed for Procedure: the retention time for fenbendazole is about 19 minutes; the relative retention time is about 0.85 for mebendazole and 1.0 for fenbendazole; and the resolution, R, between mebendazole and fenbendazole is not less than 1.5. Chromatograph Standard solution 2 and Standard solution 3, and record the peak area responses as directed for Procedure: the relative retention times are about 0.25 for fenbendazole related compound A and 0.65 for fenbendazole related compound B.
Procedure— Separately inject equal volumes (about 10 µL) of Standard solution 1, Standard solution 2, Standard solution 3, and the Test solution into the chromatograph, record the chromatograms, and measure the area responses for all of the peaks. Calculate the percentages of fenbendazole related compound A and of fenbendazole related compound B in the portion of Fenbendazole taken by the formula:
0.1(C/W)(ri / rSi)
in which C is the concentration, in mg per mL, of USP Fenbendazole Related Compound A RS or USP Fenbendazole Related Compound B RS in Standard solution 2 or Standard solution 3, as appropriate; W is the weight, in mg, of Fenbendazole taken to prepare the Test solution; ri is the peak area response of the relevant related compound obtained from the Test solution; and rSi is the peak area response of the relevant related compound obtained from Standard solution 2 or Standard solution 3, as appropriate. Not more than 0.5% of either related compound is found. Calculate the percentage of any other impurity in the portion of Fenbendazole taken by the formula:
0.1(C/W)(ri / rS)
in which C is the concentration, in mg per mL, of USP Fenbendazole RS in Standard solution 1; W is as defined above; ri is the peak area response of any impurity other than fenbendazole related compound A or fenbendazole related compound B obtained from the Test solution; and rS is the peak area response of the main peak in the chromatogram obtained from Standard solution 1. Disregard any impurity peak with a response that is less than one-fifth that of rS. Not more than 0.5% of any other impurity is found. The sum of all impurities found, including fenbendazole related compound A and fenbendazole related compound B, is not more than 1%.
Assay— Dissolve about 200 mg of Fenbendazole, accurately weighed, in 30 mL of glacial acetic acid, warming if necessary to effect solution. Cool, and titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Each mL of 0.1 N perchloric acid is equivalent to 29.94 mg of C15H13N3O2S.
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