A: Infrared Absorption 197M.

B: Ultraviolet Absorption 197U—

Solution: 10 µg per mL.

Medium: water.

C: A solution of it meets the requirements of the tests for Chloride 191.

Test solution— Prepare a solution in methanol containing 22.3 mg per mL of Ranitidine Hydrochloride.

Standard solutions— Dissolve an accurately weighed quantity of USP Ranitidine Hydrochloride RS in methanol, and dilute with methanol to obtain Standard solution A, having a known concentration of about 0.22 mg per mL. Dilute portions of Standard solution A quantitatively with methanol to obtain Standard solutions B, C, and D, having concentrations of 110, 66, and 11 µg per mL, respectively.

Resolution solution— Dissolve an accurately weighed quantity of USP Ranitidine Related Compound A RS in methanol to obtain a solution having a known concentration of about 1.27 mg per mL.

Identification preparation— Dissolve an accurately weighed quantity of USP Ranitidine Related Compound B RS in methanol to obtain a solution having a known concentration of about 1 mg per mL.

Procedure— Separately apply 10 µL each of the Test solution, each of the Standard solutions, and the Identification solution to a thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Separately apply an additional 10 µL of the Test solution to the same plate, and on top of this application, apply 10 µL of the Resolution solution. Allow the spots to dry, and develop the chromatograms in a solvent system consisting of a mixture of ethyl acetate, isopropyl alcohol, ammonium hydroxide, and water (25:15:5:1) until the solvent front has moved not less than 15 cm from the origin. Remove the plate from the developing chamber, mark the solvent front, and allow to air-dry. Expose the plate to iodine vapors in a closed chamber until the chromatogram is fully revealed. Examine the plate, and compare the intensities of any secondary spots observed in the chromatogram of the Test solution with those of the principal spots in the chromatograms of Standard solutions A, B, C, and D, and the Identification solution: the system suitability requirements are met if there is complete resolution between the primary spots in the chromatogram of the combined Test solution and Resolution solution, and if a spot is observed in the chromatogram of Standard solution D. Any spot observed in the chromatogram of the Test solution at the RF value corresponding to that of the principal spot produced by the Identification solution is not greater in size or intensity than the principal spot obtained from Standard solution B, corresponding to not more than 0.5%; and no other spot in the chromatogram of the Test solution exceeds the size or intensity of the principal spot obtained from Standard solution C (0.3%). The sum of the intensities of all secondary spots obtained from the Test solution corresponds to not more than 1.0%.

(Official January 1, 2007)

Mobile phase— Prepare a filtered and degassed mixture of methanol and 0.1 M aqueous ammonium acetate (85:15). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of USP Ranitidine Hydrochloride RS in Mobile phase to obtain a solution having a known concentration of about 0.112 mg (equivalent to 0.100 mg of ranitidine base) per mL.

System suitability solution— Dissolve accurately weighed quantities of USP Ranitidine Hydrochloride RS and USP Ranitidine Related Compound C RS in Mobile phase to obtain a solution having known concentrations of about 0.112 mg per mL and 0.01 mg per mL, respectively.

Assay preparation— Transfer about 112 mg of Ranitidine Hydrochloride, accurately weighed, to a 100-mL volumetric flask. Dissolve in and dilute with Mobile phase to volume, and mix. Transfer 1.0 mL of this solution to a 10-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 322-nm detector and a 4.6-mm × 20- to 30-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between ranitidine hydrochloride and N-[2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]sulfinyl]ethyl]-N¢-methyl-2-nitro-1,1-ethenediamine (ranitidine related compound C) is not less than 1.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for the ranitidine hydrochloride peak is not more than 2.0; the column efficiency determined from the ranitidine hydrochloride peak is not less than 700 theoretical plates; and the relative standard deviation for replicate injections is not more than 2%.

Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of C13H22N4O3S·HCl in the portion of Ranitidine Hydrochloride taken by the formula: in which C is the concentration, in mg per mL, of USP Ranitidine Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.