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Category  Anti-infective; antidiarrheal; antiflatulent; carminative.

Phenyl Salicylate and Menthol Oral Suspension contains not less than 90.0 per cent and not more than 110.0 per cent of the labelled amount of phenyl salicylate (C₁₃H₁₀O₃) and menthol (C₁₀H₂₀O). It may contain one or more suitable buffers, preservatives, sweeteners, and suspending agents.

Strength available  2 g of phenyl salicylate and 156 mg of menthol per 100 mL.

Dose  Adults: 300 mg of phenyl salicylate and 23.4 mg of menthol three times a day.

            Children: 100 mg of phenyl salicylate and 7.8 mg of menthol three times a day.

Contra-indication  It is contra-indicated in patients with history of hypersensitivity reactions to any ingredients in this medicine.

Warning  It may cause rash and urticaria.

Packaging and storage  Phenyl Salicylate and Menthol Oral Suspension shall be kept in tightly closed containers and stored at a temperature not exceeding 30º. Avoid refrigerating.

Identification

      A. The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation, as obtained in the Assay for menthol.

      B. The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation, as obtained in the Assay for phenyl salicylate.

pH  4.0 to 6.0 (Appendix 4.11).

Limit of phenol  Not more than 1.0 per cent w/w (for phenyl salicylate in the Oral Suspension). Carry out the test as described in the “Liquid Chromatography” (Appendix 3.5).

Diluent  Prepare a mixture of equal volumes of acetonitrile and a 0.03 per cent v/v solution of phosphoric acid.

Standard solution  Dissolve an accurately weighed quantity of Phenol RS, in Diluent to obtain a solution having a known concentration of 4 µg per mL.

Test solution  Transfer about 2 mL, accurately measured, of Phenyl Salicylate and Menthol Oral Suspension to a 100-mL volumetric flask, dilute with Diluent to volume, and mix.

Mobile phase

Mobile phase A  Prepare a 0.03 per cent v/v of phosphoric acid.

Mobile phase B  Acetonitrile.

The step gradient of mobile phases is as follow.

Chromatographic System

Detector  Ultraviolet light (275 nm).

Column  A stainless steel column (75 mm × 4.6 mm), packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (3.5 µm).

Temperature  

   Column  About 35º.

Flow rate  2.0 mL per minute.

System Suitability

Sample  Standard solution. 

Suitability requirements 

Symmetry factor  Not more than 2.0.

Relative standard deviation  Not more than 2.0 per cent.

COLUMN EFFICIENCY  Not less than 2,000 theoretical plates. 

Procedure  Separately inject equal volumes (about 10 µL) of Standard solution and Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peak. Identify the peak due to phenol in the test solution, using the retention time of phenol in the standard solution.

Calculation  Calculate the percentage of phenol (C₆H₆O) in the portion of the Oral Suspension taken by the expression,

(Au/As)(Cs/Cu) x 100

in which Au and As are the peak areas due to phenol obtained from Test solution and Standard solution, respectively; Cs is the concentration of phenol, in mg per mL, in the standard solution; Cu is the concentration of phenyl salicylate, in mg per mL, in the test solution.

Microbial limit  Complies with the requirements for Category 4A in “Limits for Microbial Contamination” (Appendix 10.5).

 Assay

For phenyl salicylate  Carry out the determination as described in the “Liquid Chromatography” (Appendix 3.5).

Diluent; Mobile phase  Prepare a mixture of equal volumes of acetonitrile and a 0.03 per cent v/v solution of phosphoric acid.

Standard preparation  Dissolve an accurately weighed quantity of Phenyl Salicylate RS, quantitatively in Diluent to obtain a solution having a known concentration of 400 µg per mL.

Assay preparation  Transfer an accurately weighed or measured portion of Phenyl Salicylate and Menthol Oral Suspension, containing about 40 mg of phenyl salicylate to a 100-mL volumetric flask, and dilute with Diluent to volume. Mix and filter through a 0.45-µm membrane filter.

Chromatographic System

Detector  Ultraviolet light (275 nm).

Column  A stainless steel column (75 mm × 4.6 mm), packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (3.5 µm).

Temperature  

   Column  About 30º.

Flow rate  2.0 mL per minute.

System Suitability

Sample  Standard preparation. 

Suitability requirements 

Symmetry factor  Not more than 2.0.

Relative standard deviation  Not more than 2.0 per cent.

COLUMN EFFICIENCY  Not less than 2,000 theoretical plates.

Procedure  Separately inject equal volumes (about 10 µL) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks.

Calculation  Calculate the content of C₁₃H₁₀O₃ in the portion of the Oral Suspension taken, using the declared content of C₁₃H₁₀O₃ in Phenyl Salicylate RS.

For Menthol  Carry out the determination as described in the “Liquid Chromatography” (Appendix 3.5).

Diluent  Acetonitrile and water (75:25).

Standard preparation  Dissolve an accurately weighed quantity of Menthol RS, quantitatively in Diluent to obtain a solution having a known concentration of 312 µg per mL.

Assay preparation  Transfer about 10 g of Phenyl Salicylate and Menthol Oral Suspension, accurately weighed, to a 50-mL volumetric flask. Add 1.0 mL of 1 M hydrochloric acid and mix. Add 30 mL of Diluent and then sonicate for 20 minutes. Allow to cool. Add 1.0 mL of 1 M sodium hydroxide, dilute with Diluent to volume, and mix.

Mobile phase  Prepare a mixture of 55 volumes of acetonitrile and 45 volumes of a 0.2 v/v solution of triethanolamine, adjusted to pH 5 with glacial acetic acid.

Chromatographic system

Detector  A refractive index detector.

Column  A stainless steel column (150 mm × 4.6 mm), packed with octylsilane chemically bonded to porous silica or ceramic microparticles (5 µm).

Temperature

  Detector 50º.

  Column 50º.

Flow rate  1.0 mL per minute.

System Suitability

Sample  Standard preparation. 

Suitability requirements

Symmetry factor  Not more than 2.0.

Relative standard deviation  Not more than 2.0 per cent.

COLUMN EFFICIENCY  Not less than 2,000 theoretical plates.

Procedure  Separately inject equal volumes (about 50 µL) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks.

Calculation  Calculate the quantity, in mg, of menthol (C₁₀H₂₀O) in each mL of the Oral Suspension taken by the expression:

(dW/w)(Au/As),

in which d is the weight per mL of the Oral Suspension determined as described in Appendix 4.9; W and w are the weights, in mg, of Menthol RS and the Oral Suspension taken, respectively; and Au and As are the peak areas due to menthol obtained from Assay preparation and Standard preparation, respectively.

Other requirements  Complies with the requirements described under “Oral Liquids” (Appendix 1.16).