Erythromycin Estolate and Sulfisoxazole Acetyl Oral Suspension
»Erythromycin Estolate and Sulfisoxazole Acetyl Oral Suspension contains the equivalent of not less than 90.0percent and not more than 120.0percent of the labeled amount of erythromycin (C37H67NO13)and the equivalent of not less than 90.0percent and not more than 115.0percent of the labeled amount of sulfisoxazole (C11H13N3O3S).It contains one or more suitable buffers,colors,diluents,emulsifiers,flavors,preservatives,and suspending agents.
Packaging and storage— Preserve in tight containers.
Identification— To a quantity of the Oral Suspension add a volume of methanol sufficient to yield a solution having a concentration equivalent to about 2.5mg of erythromycin per mL.Shake this mixture by mechanical means for about 30minutes.Centrifuge a portion of this mixture,and use the clear supernatant as the test solution.Prepare a solution of USP Erythromycin Estolate RSin methanol containing about 3mg per mL(Standard solution A).Prepare a solution of USP Sulfisoxazole Acetyl RSin methanol containing about 8.7mg per mL(Standard solution B).Apply separately 10µLeach of the test solution and the two Standard solutions to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture,and allow to dry.Place the plate in an unlined chromatographic chamber,and develop the chromatograms in a solvent system consisting of a mixture of methanol and chloroform (85:15)until the solvent front has moved about 9cm.Remove the plate from the chamber,mark the solvent front,and allow the solvent to evaporate.Spray the plate with a mixture of dehydrated alcohol,p-methoxybenzaldehyde,and sulfuric acid (90:5:5).Heat the plate at 100for 10minutes,and examine the chromatograms,in which the erythromycin estolate appears as a black-to-purple spot and the sulfisoxazole acetyl appears as a yellow spot:the RFvalue of the principal black-to-purple spot obtained from the test solution corresponds to that obtained from Standard solution A,and the RFvalue of the principal yellow spot obtained from the test solution corresponds to that obtained from Standard solution B.
Uniformity of dosage units á905ñ—
FORSUSPENSION PACKAGED IN SINGLE-UNIT CONTAINERS :meets the requirements.
Deliverable volume á698ñ: meets the requirements.
pHá791ñ: between 3.5and 6.5.
Assay for erythromycin— Dilute an accurately measured volume of Oral Suspension,freshly mixed and free from air bubbles,quantitatively with methanol to obtain a solution containing the equivalent of 2.5mg of erythromycin per mL.Dilute with 1.5volumes of Buffer No.3,and allow to stand at room temperature for 18hours.Proceed as directed for erythromycin under Antibiotics—Microbial Assays á81ñ,using an accurately measured volume of this stock test solution diluted quantitatively with Buffer No.3to yield a Test Dilutionhaving a concentration assumed to be equal to the median dose level of the Standard (1.0µg of erythromycin per mL).
Assay for sulfisoxazole—
Mobile solvent— Mix 40volumes of acetonitrile and 60volumes of water.The acetonitrile concentration may be varied to meet system suitability requirements and to provide a suitable elution time for sulfisoxazole acetyl.Filter the solution through a membrane filter (1-µm or finer porosity).
Internal standard solution— Prepare a solution of benzanilide in acetonitrile having a concentration of about 0.33mg per mL.Filter the solution through a membrane filter (1-µm or finer porosity).
Standard preparation— Prepare a solution of USP Sulfisoxazole Acetyl RSin Internal standard solutionhaving a known concentration of about 1mg per mL.
Assay preparation— Transfer an accurately measured volume of Oral Suspension,freshly mixed and free from air bubbles,equivalent to about 600mg of sulfisoxazole,to a 125-mLseparator,and extract with three 75-mLportions of chloroform.Collect the chloroform extracts in a 250-mLvolumetric flask,dilute with chloroform to volume,and mix.Filter a portion of this solution through a membrane filter (1-µm or finer porosity).Pipet 4mLof the filtrate into a glass-stoppered,25-mLconical flask,and evaporate with the aid of a current of dry air to dryness.Add 10.0mLof Internal standard solution,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4-mm ×30-cm column that contains packing L1.The flow rate is about 1.2mLper minute.Chromatograph replicate injections of the Standard preparation,and record the peak responses as directed under Procedure:the resolution factor between sulfisoxazole acetyl and benzanilide is not less than 3.0.
Procedure— Separately inject equal volumes (about 5µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of sulfisoxazole (C11H13N3O3S)in each mLof the Oral Suspension taken by the formula:
(267.31/309.35)(625C/V)(RU/RS),
in which 267.31and 309.35are the molecular weights of sulfisoxazole and sulfisoxazole acetyl,respectively;Cis the concentration,in mg,of USP Sulfisoxazole Acetyl RSin each mLof the Standard preparation;Vis the volume,in mL,of Oral Suspension taken;and RUand RSare the ratios of peak responses of sulfisoxazole acetyl peak to benzanilide peak obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:William W.Wright,Ph.D.,Scientific Fellow
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 764
Phone Number:1-301-816-8335