»Ranitidine Hydrochloride contains not less than 97.5percent and not more than 102.0percent of C13H22N4O3S·HCl,calculated on the dried basis.
Packaging and storage Preserve in tight,light-resistant containers.
USP Reference standards á11ñ USP Ranitidine Hydrochloride RS.USP Ranitidine Related Compound A RS.USP Ranitidine Related Compound B RS.USP Ranitidine Related Compound C RS.
A: Infrared Absorption á197Mñ.
Solution: 10µg per mL.
Absorptivities at 229nm and 315nm,calculated on the dried basis,do not differ by more than 3.0%.
C: Asolution of it meets the requirements of the tests for Chloride á191ñ.
pHá791ñ: between 4.5and 6.0,in a solution (1in 100).
Loss on drying á731ñ Dry it in vacuum at 60for 3hours:it loses not more than 0.75%of its weight.
Residue on ignition á281ñ: not more than 0.1%.
Test solution Prepare a solution in methanol containing 22.3mg per mLof Ranitidine Hydrochloride.
Standard solutions Dissolve an accurately weighed quantity of USP Ranitidine Hydrochloride RSin methanol,and dilute with methanol to obtain Standard solution A,having a known concentration of about 0.22mg per mL.Dilute portions of Standard solution Aquantitatively with methanol to obtain Standard solutions B,C,and D,having concentrations of 110,66,and 11µg per mL,respectively.
Resolution solution Dissolve an accurately weighed quantity of USP Ranitidine Related Compound A RSin methanol to obtain a solution having a known concentration of about 1.27mg per mL.
Identification preparation Dissolve an accurately weighed quantity of USP Ranitidine Related Compound B RSin methanol to obtain a solution having a known concentration of about 1mg per mL.
Procedure Separately apply 10µLeach of the Test solution,each of the Standard solutions,and the Identification solutionto a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Separately apply an additional 10µLof the Test solutionto the same plate,and on top of this application,apply 10µLof 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 15cm 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 solutionwith 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 solutionand Resolution solution,and if a spot is observed in the chromatogram of Standard solution D.Any spot observed in the chromatogram of the Test solutionat the RFvalue corresponding to that of the principal spot produced by the Identification solutionis 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 solutionexceeds 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 solutioncorresponds to not more than 1.0%.
Organic volatile impurities,Method IVá467ñ: meets the requirements.
Mobile phase Prepare a filtered and degassed mixture of methanol and 0.1Maqueous ammonium acetate (85:15).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation Dissolve an accurately weighed quantity of USP Ranitidine Hydrochloride RSin Mobile phaseto obtain a solution having a known concentration of about 0.112mg (equivalent to 0.100mg of ranitidine base)per mL.
System suitability solution Dissolve accurately weighed quantities of USP Ranitidine Hydrochloride RSand USP Ranitidine Related Compound C RSin Mobile phaseto obtain a solution having known concentrations of about 0.112mg per mLand 0.01mg per mL,respectively.
Assay preparation Transfer about 112mg of Ranitidine Hydrochloride,accurately weighed,to a 100-mLvolumetric flask.Dissolve in and dilute with Mobile phaseto volume,and mix.Transfer 1.0mLof this solution to a 10-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)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 2mLper 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 700theoretical plates;and the relative standard deviation for replicate injections is not more than 2%.
Procedure Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto 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:
1000C(rU/rS),in which Cis the concentration,in mg per mL,of USP Ranitidine Hydrochloride RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28NF23Page 1702Pharmacopeial Forum:Volume No.29(5)Page 1569