Cimetidine Hydrochloride
(sye met' i deen hye'' droe klor' ide).
C10H16N6S·HCl 288.81

Guanidine, N ¢¢-cyano-N-methyl-N¢-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]thio]ethyl]-, monohydrochloride.
2-Cyano-1-methyl-3-[2-[[(5-methylimidazol-4-yl)methyl]thio]ethyl]guanidine monohydrochloride [70059-30-2].
» Cimetidine Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C10H16N6S·HCl, calculated on the dried basis.
Packaging and storage— Preserve in tight, light-resistant containers.
USP Reference standards 11
USP Cimetidine Hydrochloride RS Click to View Structure
Identification—
Solution: 14 µg per mL.
Medium: 0.1 N sulfuric acid.
Loss on drying 731 Dry it at 105 for 2 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.2%.
Chromatographic purity—
Mobile phase— Transfer about 940 mg of sodium 1-hexanesulfonate to a 1000-mL volumetric flask, add 240 mL of methanol followed by 0.3 mL of phosphoric acid, and dilute with water to volume. Mix, and filter. Make adjustments if necessary (see System Suitability under Chromatography 621).
Test solution 1— Transfer about 100 mg of Cimetidine Hydrochloride, accurately weighed, to a 250-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Test solution 2— Transfer 1.0 mL of Test solution 1 to a 500-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Resolution solution— Dissolve about 50 mg of Cimetidine Hydrochloride in 10 mL of 1 N hydrochloric acid, and heat on a steam bath for about 10 minutes (or boil on a hot plate for about 2 minutes), and allow to cool. Dilute a suitable volume of this solution with Mobile phase to obtain a solution having a concentration of about 2 µg per mL. [note—Use this solution within 24 hours of its preparation. Adjustment of the heating step may be necessary to achieve a satisfactory amide analog peak response for the measurement of the resolution between the cimetidine and the amide analog peaks. ]
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between the cimetidine and the amide analog peaks is not less than 4.0. Chromatograph Test solution 2, and record the peak responses as directed for Procedure: the capacity factor, k¢, is not less than 3.0; the column efficiency is not less than 2000 theoretical plates; and the relative standard deviation for replicate injections is not more than 7.0%.
Procedure— Separately inject equal volumes (about 50 µL) of Test solution 1 and Test solution 2 into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity in the portion of Cimetidine Hydrochloride taken by the formula:
0.2(ri / rS)
in which ri is the peak response for an individual impurity observed in the chromatogram obtained from Test solution 1, and rS is the peak response of cimetidine in the chromatogram obtained from Test solution 2: no single impurity is greater than 0.2%, and the sum of all impurities is not more than 1.0%.
Assay—
Mobile phase— Transfer 200 mL of methanol and 0.3 mL of phosphoric acid to a 1000-mL volumetric flask, dilute with water to volume, mix, and filter. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Cimetidine Hydrochloride RS in a mixture of water and methanol (80:20) to obtain a solution having a known concentration of about 0.5 mg per mL. Transfer 5.0 mL of this solution to a 200-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Assay preparation— Transfer about 115 mg of Cimetidine Hydrochloride, accurately weighed, to a 250-mL volumetric flask, dissolve in about 50 mL of water, add 50 mL of methanol, and dilute with water to volume. Transfer 5.0 mL of this solution to a 200-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 220-nm detector and a 3.9-mm × 30-cm column that contains 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 capacity factor, k¢, is not less than 0.6; the column efficiency determined from the analyte peak is not less than 1000 theoretical plates; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity, in mg, of C10H16N6S·HCl in the portion of Cimetidine Hydrochloride taken by the formula:
10C(rU / rS)
in which C is the concentration, in µg per mL, of USP Cimetidine Hydrochloride RS in the Standard preparation; and rU and rS are the cimetidine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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Monograph Elena Gonikberg, Ph.D.
Principal Scientific Liaison
1-301-816-8251
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