Diltiazem Hydrochloride Tablets
DEFINITION
Diltiazem Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of diltiazem hydrochloride (C22H26N2O4S·HCl).
IDENTIFICATION
• A. Procedure
Indicator solution:
Transfer 17.4 g of ammonium thiocyanate and 2.8 g of cobalt chloride to a 100-mL volumetric flask, add 50 mL of water, and sonicate for 10 min. Dilute with water to volume.
Analysis:
Finely powder 1 Tablet, and transfer to a 15-mL screw-capped test tube. Add 10 mL of 0.1 N hydrochloric acid, shake, and filter. Add 2 mL of Indicator solution to 2 mL of the filtrate, and shake. Add 5 mL of chloroform, and shake.
Acceptance criteria:
A blue color develops in the chloroform layer.
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Solution A:
Dissolve 1.16 mg/mL of d-10-camphorsulfonic acid in 0.1 M sodium acetate, and adjust with 0.1 N sodium hydroxide to a pH of 6.2.
Mobile phase:
Acetonitrile, methanol, and Solution A (1:1:2)
Standard solution:
1.2 mg/mL of USP Diltiazem Hydrochloride RS in methanol
Sample solution:
Transfer an equivalent to 600 mg of diltiazem hydrochloride from finely powdered Tablets (NLT 20) to a 500-mL volumetric flask. Add 200 mL of methanol, and sonicate for 1 h. Cool, and dilute with methanol to volume. Centrifuge a 25-mL aliquot at 3500 rpm for 15 min, and use the clear supernatant.
System suitability solution:
12 µg/mL of USP Diltiazem Hydrochloride RS and 12 µg/mL of USP Desacetyl Diltiazem Hydrochloride RS, in methanol
Chromatographic system
Mode:
LC
Detector:
UV 240 nm
Column:
3.9-mm × 30-cm; packing L1
Flow rate:
1.6 mL/min
Injection size:
10 µL
System suitability
Samples:
Standard solution and System suitability solution
[Note—The relative retention times for desacetyl diltiazem and diltiazem are about 0.65 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 3 between desacetyl diltiazem and diltiazem, System suitability solution
Column efficiency:
NLT 1200 theoretical plates for the diltiazem peak, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C22H26N2O4S·HCl in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Diltiazem Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of diltiazem hydrochloride in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
Water; 900 mL
Apparatus 2:
75 rpm
Time:
30 min and 3 h
Detector:
UV 237 nm
Standard solution:
USP Diltiazem Hydrochloride RS in Medium
Sample solution:
Sample per Dissolution 711. Dilute with Medium to a concentration that is similar to the Standard solution.
711. Dilute with Medium to a concentration that is similar to the Standard solution.
Tolerances:
Use the following acceptance criteria for the 30-min time point: at S1 no unit is more than Q; at S2 the average value is equal to or less than Q, and no unit is greater than Q + 10%; at S3 the average value is equal to or less than Q, and not more than 2 units are more than Q + 10%, and no unit is more than Q + 25%. Use the criteria in Dissolution 711, Acceptance Table 1 for the 3-h time point. NMT 60% (Q) of the labeled amount of C22H26N2O4S·HCl is dissolved in 30 min, and NLT 75% (Q) is dissolved in 3 h.
711, Acceptance Table 1 for the 3-h time point. NMT 60% (Q) of the labeled amount of C22H26N2O4S·HCl is dissolved in 30 min, and NLT 75% (Q) is dissolved in 3 h.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers.
• USP Reference Standards 11
11
USP Desacetyl Diltiazem Hydrochloride RS
C20H24N2O3S·HCl 408.95
C20H24N2O3S·HCl 408.95
USP Diltiazem Hydrochloride RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison 1-301-816-8349 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2921
Pharmacopeial Forum: Volume No. 35(6) Page 1453