(Official January 1, 2007)

pH 4.4 Sodium phosphate buffer— Dissolve 7.8 g of monobasic sodium phosphate in 900 mL of water, adjust with phosphoric acid or 10 N sodium hydroxide to a pH of 4.4 ± 0.1, dilute with water to 1000 mL, and mix.

Mobile phase— Prepare a suitable mixture of pH 4.4 Sodium phosphate buffer and methanol (95:5), and pass through a filter having a 0.5-µm or finer porosity. Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve accurately weighed quantities of USP Amoxicillin RS and USP Clavulanate Lithium RS in water to obtain a solution having known concentrations of about 0.5 mg per mL and 0.2 mg per mL, respectively.

Assay preparation— Dilute an accurately measured volume of Amoxicillin and Clavulanic Acid for Oral Suspension, constituted as directed in the labeling, quantitatively with water to obtain a solution containing about 0.5 mg of amoxicillin per mL. Stir by mechanical means for 10 minutes, and filter. Use the filtrate as the Assay preparation within 1 hour of the dilution of the suspension.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 220-nm detector and a 4-mm × 30-cm column that contains 3- to 10-µm packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution, R, between the amoxicillin and clavulanic acid peaks is not less than 3.5; the column efficiency determined from each analyte peak is not less than 550 theoretical plates; the tailing factor for each analyte peak is not more than 1.5; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.5 for clavulanic acid and 1.0 for amoxicillin. Calculate the quantity, in mg, of amoxicillin (C16H19N3O5S) in each mL of the constituted Amoxicillin and Clavulanate Potassium for Oral Suspension taken by the formula: in which C is the concentration, in mg per mL, of USP Amoxicillin RS in the Standard preparation; P is the potency, in µg of amoxicillin per mg, of USP Amoxicillin RS; L is the labeled quantity, in mg per mL, of amoxicillin in the constituted Amoxicillin and Clavulanate Potassium for Oral Suspension; D is the concentration, in mg per mL, of amoxicillin in the Assay preparation on the basis of the labeled quantity of amoxicillin in the constituted Amoxicillin and Clavulanate Potassium for Oral Suspension, the volume of constituted Oral Suspension taken, and the extent of dilution; and rU and rS are the amoxicillin peak responses obtained from the Assay preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of clavulanic acid (C8H9NO5) in each mL of the constituted Amoxicillin and Clavulanate Potassium for Oral Suspension taken by the formula: in which L is the labeled quantity, in mg per mL, of clavulanic acid in the constituted Amoxicillin and Clavulanate Potassium for Oral Suspension; D is the concentration, in mg per mL, of clavulanic acid in the Assay preparation on the basis of the labeled quantity of clavulanic acid in the constituted Oral Suspension, the volume of constituted Oral Suspension taken, and the extent of dilution; C is the concentration, in mg per mL, of USP Clavulanate Lithium RS in the Standard preparation; P is the designated potency, in µg of clavulanic acid per mg, of the USP Clavulanate Lithium RS; and rU and rS are the clavulanic acid peak responses obtained from the Assay preparation and the Standard preparation, respectively.