Benzocaine and Menthol Topical Aerosol
» Benzocaine and Menthol Topical Aerosol is a solution of Benzocaine and Menthol with suitable propellants in a pressurized container. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of benzocaine (C9H11NO2) and menthol (C10H20O).
Packaging and storage— Preserve in tight, pressurized containers, and avoid exposure to excessive heat.
USP Reference standards 11
USP Benzocaine RS Click to View Structure
USP Menthol RS Click to View Structure
Identification—
A: Transfer an amount of Topical Aerosol, equivalent to about 5 mg of benzocaine, to a beaker, add 20 mL of 0.5 N hydrochloric acid, warm gently to disperse the solution, cool, and filter, if necessary, to obtain a clear solution. To 10 mL of the clear solution add 5 drops of a solution of sodium nitrite (1 in 10), and 2 drops of methyl red TS, and neutralize with 1 N sodium hydroxide. Add 2 mL of a solution of 100 mg of 2-naphthol in 5 mL of 1 N sodium hydroxide: an orange-red precipitate is formed.
B: The retention time of the major peak for benzocaine in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay for benzocaine.
C: The retention time of the major peak for menthol in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay for menthol.
Microbial enumeration tests 61 and Tests for specified microorganisms 62 It meets the requirements of the tests for absence of Staphylococcus aureus and Pseudomonas aeruginosa.
Minimum fill 755: meets the requirements.
Other requirements— It meets the requirements for the Leakage Test and the Pressure Test under Aerosols, Nasal Sprays, Metered-Dose Inhalers, and Dry Powder Inhalers 601.
Assay for benzocaine—
Diluent— Prepare a mixture of methanol and water (1:1).
Mobile phase— Prepare a mixture of methanol, water, and glacial acetic acid (56:40:4). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Prepare a solution of USP Benzocaine RS in Diluent having a known concentration of about 0.02 mg per mL.
Assay preparation— Spray the Topical Aerosol into a flask. Transfer an accurately measured volume of the solution, equivalent to about 200 mg of benzocaine, to a 100-mL volumetric flask, dilute with Diluent to volume, and mix. Transfer 1.0 mL of this solution to a second 100-mL volumetric flask, dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 294-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 50 µL) of the Assay preparation and the Standard preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of benzocaine (C9H11NO2) in the portion of Topical Aerosol taken by the formula:
10,000C(rU / rS)
in which C is the concentration, in mg per mL, of USP Benzocaine RS in the Standard preparation, and rU and rS are the benzocaine peak areas obtained from the Assay preparation and the Standard preparation, respectively.
Assay for menthol—
Internal standard solution— Dissolve decanol in n-hexane to obtain a solution having a concentration of about 1 mg per mL.
Standard preparation— Dissolve an accurately weighed quantity of USP Menthol RS in n-hexane to obtain a solution having a known concentration of about 1 mg per mL. Transfer 5.0 mL of this solution and 5.0 mL of Internal standard solution to a 100-mL volumetric flask, dilute with ether to volume, and mix.
Assay preparation— Spray the Topical Aerosol into a flask. Transfer an accurately measured volume of the solution, equivalent to about 50 mg of menthol, to a separator, and extract with three 15-mL portions of ether, collecting the ether extracts in a 50-mL volumetric flask. Dilute with ether to volume, and mix. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, add 5.0 mL of n-hexane and 5.0 mL of Internal standard solution, dilute with ether to volume, and mix.
Chromatographic system (see Chromatography 621)—The gas chromatograph is equipped with a flame-ionization detector and contains a 2-mm × 1.8-m column packed with 10% phase G16 on support S1AB. The column temperature is maintained isothermally at about 170, the injection port temperature is maintained at about 260, and the detector block temperature is maintained at about 240. Dry helium is used as the carrier gas at a flow rate of about 50 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for menthol and 1.0 for decanol; the resolution, R, between the menthol peak and the decanol peak is not less than 2.5; and the relative standard deviation of the ratio of the peak response obtained with menthol to that obtained with decanol is not more than 2%.
Procedure— Separately inject equal volumes (about 2 µL) of the Assay preparation and the Standard preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of menthol (C10H20O) in each mL of Topical Aerosol taken by the formula:
1000(C / V)(RU / RS)
in which C is the concentration, in mg per mL, of USP Menthol RS in the Standard preparation; V is the volume, in mL, of Topical Aerosol taken; and RU and RS are the peak response ratios of menthol to decanol obtained from the Assay preparation and the Standard preparation, respectively.
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Monograph Ravi Ravichandran, Ph.D.
Principal Scientific Liaison
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(SM42010) Monographs - Small Molecules 4
Reference Standards RS Technical Services
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61 Radhakrishna S Tirumalai, Ph.D.
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(GCM2010) General Chapters - Microbiology
62 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
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(GCM2010) General Chapters - Microbiology
USP35–NF30 Page 2324