Identification
B:
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chormatogram of the Standard preparation, obtained as directed in the Assay.
C:
It responds to the tests for
Chloride 191.
Related compounds
Buffer
and Mobile phasePrepare as directed in the Assay.
Standard solution
Use the System suitability preparation prepared as directed under Assay.
Test solution
Prepare as directed for the Assay preparation in the Assay.
Chromatographic system
Prepare as directed under Assay. The relative standard deviation of the peak response for replicate injections of the Standard solution is not more than 10.0%.
Procedure
Separately inject equal volumes (about 10 µL) of the
Standard solution and the
Test solution into the chromatograph, record the chromatograms, and measure the responses for all of the peaks. The relative retention times are about 0.65 for desacetyl diltiazem and 1.0 for diltiazem. Calculate the percentage of desacetyl diltiazem hydrochloride in the specimen of Diltiazem Hydrochloride taken by the formula:
10(C / W)(rU / rS),
in which
C is the concentration, in µg per mL, of
USP Desacetyl Diltiazem Hydrochloride RS in the
Standard solution,
W is the weight, in mg, of Diltiazem Hydrochloride taken, and
rU and
rS are the desacetyl diltiazem peak responses obtained from the
Test solution and the
Standard solution, respectively: not more than 0.5% of desacetyl diltiazem hydrochloride is found. Calculate the percentage of each impurity peak, other than the main peak and the desacetyl diltiazem peak, by the formula:
10(C / W)(rI / rS),
in which
rI is the response of each impurity peak and all other quantities are as defined above: not more than 1.0% total impurities including desacetyl diltiazem hydrochloride with no individual impurity greater than 0.5% is found.
Assay
Buffer
Dissolve 1.16 g of d-10-camphorsulfonic acid in 1000 mL of 0.1 M sodium acetate, adjust this solution by the addition of 0.1 N sodium hydroxide to a pH of 6.2, and mix.
Mobile phase
Prepare a mixture of
Buffer, acetonitrile, and methanol (50:25:25), filter, and degas. Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard preparation
Prepare a solution in methanol having an accurately known concentration of about 1.2 mg of
USP Diltiazem Hydrochloride RS per mL.
Assay preparation
Transfer about 120 mg of Diltiazem Hydrochloride, accurately weighed, to a 100-mL volumetric flask, dissolve in methanol, dilute with methanol to volume, and mix.
Chromatographic system
The liquid chromatograph is equipped with a 240-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 1.6 mL per minute. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.65 for desacetyl diltiazem and 1.0 for diltiazem, the resolution, R, between desacetyl diltiazem and diltiazem is not less than 3, and the number of theoretical plates, n, for the diltiazem peak is not less than 1200. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
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 responses for the major peaks. Calculate the quantity, in mg, of C
22H
26N
2O
4S·HCl in the Diltiazem Hydrochloride taken by the formula:
100C(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Diltiazem Hydrochloride RS in the
Standard preparation, and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.