Diltiazem Hydrochloride Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Diltiazem Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of diltiazem hydrochloride (C₂₂H₂₆N₂O₄S · HCl).

2 IDENTIFICATION

A. The UV-Vis spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Solution A: 0.79 g/L of ammonium bicarbonate in water. Adjust with diluted ammonia solution to a pH of 8.0.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (40:60)

Standard solution: 0.05 mg/mL of USP Diltiazem Hydrochloride RS in Diluent

Sample stock solution: Nominally 0.5 mg/mL of diltiazem hydrochloride from Tablets in Diluent prepared as follows. Transfer an appropriate portion of finely powdered Tablets (NLT 20) to a suitable volumetric flask. Add Diluent equivalent to 80% of the flask volume, and sonicate for 60 min. Dilute with Diluent to volume. Centrifuge the solution for 20 min. Use the supernatant.

Sample solution: Nominally 0.05 mg/mL of diltiazem hydrochloride in Diluent from Sample stock solution

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 240 nm. For Identification test A, use a diode-array detector in the range of 190–400 nm.
• Column: 2.1-mm × 15-cm; 1.7-µm packing L1
• Flow rate: 0.3 mL/min
• Injection volume: 2.0 µL

System suitability

• Sample: Standard solution
• Suitability requirements:
• Tailing factor: NMT 2.0
• Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of diltiazem hydrochloride (C₂₂H₂₆N₂O₄S · HCl) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of diltiazem from the Sample solution

rₛ = peak response of diltiazem 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%

4 PERFORMANCE TESTS

4.1 Dissolution 〈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.

Tolerances: See Table 2 for the 30-min time point. Use the criteria in Dissolution (711), Acceptance Table 1 for the 3-h time point. NMT 60% (Q) of the labeled amount of diltiazem hydrochloride (C₂₂H₂₆N₂O₄S · HCl) is dissolved in 30 min, and NLT 75% (Q) is dissolved in 3 h.

Table 2

4.2 Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 2.5 µg/mL each of USP Desacetyl Diltiazem Hydrochloride RS and USP Diltiazem Hydrochloride RS in Diluent

Sample solution: Nominally 0.5 mg/mL of diltiazem hydrochloride from Tablets in Diluent prepared as follows. Transfer an appropriate portion of the powdered Tablets (NLT 20) to a suitable volumetric flask. Add Diluent equivalent to 80% of the flask volume, and sonicate for 60 min. Dilute with Diluent to volume. Centrifuge the solution for 20 min. Use the supernatant.

System suitability

• Sample: Standard solution
• [NOTE-See Table 3 for the relative retention times.)
• Suitability requirements
• Resolution: NLT 2.0 between desacetyl diltiazem and diltiazem
• Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of desacetyl diltiazem in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of desacetyl diltiazem from the Sample solution 

rₛ = peak response of desacetyl diltiazem from the Standard solution

Cₛ = concentration of USP Desacetyl Diltiazem Hydrochloride RS in the Standard solution (µg/mL)

Cᵤ = nominal concentration of diltiazem hydrochloride in the Sample solution (µg/mL)

Calculate the percentage of any individual unspecified impurity in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of each unspecified impurity from the Sample solution

rₛ = peak response of diltiazem from the Standard solution

Cₛ = concentration of USP Diltiazem Hydrochloride RS in the Standard solution (µg/mL)

Cᵤ = nominal concentration of diltiazem hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 3. The disregard limit is 0.05%.

Table 3

ᵃ (2S,3S)-5-(2-Aminoethyl)-3-hydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-1,5-benzothiazepine-4(5H)-one.

ᵇ (2S,3S)-3-Hydroxy-2-(3-methoxyphenyl)-5-[2-(methylamino)ethyl]-2,3-dihydrobenzo[b][1,4]thiazepin-4(5H)-one.

ᶜ (2S,3S)-5-[2-(Dimethylamino)ethyl]-2-(4-hydroxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate.

ᵈ (2S,3S)-2-(4-Methoxyphenyl)-5-[2-(methylamino)ethyl]-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-3-yl acetate.

ᵉ (2S,3S)-3-Hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepine-4(5H)-one.

ᶠ (2R,3S)-5-[2-(Dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-3-yl acetate.

ᵍ (2S,3S)-2-(4-Methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-3-yl acetate.

ʰ These are impurities related to the drug substance. They are not to be reported for the drug product and should not be included in the total impurities.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Desacetyl Diltiazem Hydrochloride RS

C₂₀H₂₄N₂O₃S · HCl        408.94

USP Diltiazem Hydrochloride RS