(ver ap' a mil hye'' droe klor' ide).
Benzeneacetonitrile, -[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy--(1-methylethyl)-, monohydrochloride, (±)-.
(±)-5-[(3,4-Dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile monohydrochloride [152-11-4].
» Verapamil Hydrochloride contains not less than 99.0 percent and not more than 101.0 percent of C27H38N2O4·HCl, calculated on the dried basis.
Packaging and storage Preserve in tight, light-resistant containers. Store at 25, excursions permitted between 15 and 30.
USP Reference standards 11
B: The retention time of the major peak for verapamil in the chromatogram of the Test preparation corresponds to that exhibited in the chromatogram of Standard preparation B, as obtained in the test for Chromatographic purity.
C: It responds to the tests for Chloride 191.
Melting range 741: between 140 and 144.
pH 791: between 4.5 and 6.5, in a solution, prepared with gentle heating, containing 50 mg per mL.
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 0.1%.
Aqueous solvent mixture Prepare a 0.015 N sodium acetate solution containing about 33 mL of glacial acetic acid per L.
Mobile phase Prepare a filtered and degassed mixture of Aqueous solvent mixture, acetonitrile, and 2-aminoheptane (70:30:0.5). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparations Dissolve an accurately weighed quantity ofUSP Verapamil Hydrochloride RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain Standard preparation A and Standard preparation B having known concentrations of about 5.6 and 9.4 µg per mL, respectively.
Test preparation Prepare a solution of Verapamil Hydrochloride in Mobile phase having a known concentration of about 1.9 mg per mL.
System suitability solution Dissolve suitable quantities ofUSP Verapamil Hydrochloride RS and USP Verapamil Related Compound B RS in Mobile phase to obtain a System suitability solution having known concentrations of about 1.9 and 1.5 mg, respectively, in each mL.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 278-nm detector and a 4.6-mm × 12.5- to 15-cm column that contains packing L1. The flow rate is about 0.9 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.88 for verapamil related compound B and 1.0 for verapamil; the resolution, R, between the verapamil related compound B and verapamil peaks is not less than 1.5, and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 10 µL) of Standard preparations A and B and the Test preparation into the chromatograph, and allow the Test preparation to elute for not less than four times the retention time for verapamil. Record the chromatograms, and measure all the peak responses. The sum of the peak responses, other than that of verapamil, from the Test preparation is not greater than the verapamil peak response obtained from Standard preparation B (0.5%); and no single peak response is greater than that of the verapamil peak response obtained from Standard preparation A (0.3%).
Assay Dissolve about 400 mg of Verapamil Hydrochloride, accurately weighed, in 40 mL of glacial acetic acid; and add 10 mL of mercuric acetate TS and 5 mL of acetic anhydride. Titrate (see Titrimetry 541) with 0.10 N perchloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction. Each mL of 0.10 N perchloric acid is equivalent to 49.11 mg of C27H38N2O4·HCl.
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USP35NF30 Page 5011Pharmacopeial Forum: Volume No. 33(5) Page 953