Diltiazem Hydrochloride

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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C₂₂H₂₆N₂O₄S · HCl 450.98

1,5-Benzothiazepin-4(5H)-one, 3-(acetyloxy)-5-[2-(dimethyl amino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-, monohydrochloride, (+)-cis-;

(2S,3S)-5-[2-(Dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetate monohydrochloride CAS RN®: 33286-22-5; UNII: OLH94387TE.

1 DEFINITION

Diltiazem Hydrochloride contains NLT 98.0% and NMT 102.0% of diltiazem hydrochloride (C₂₂H₂₆N₂O₄S · HCl), calculated on the dried basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

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

C. Identification Tests-General Chloride 〈191〉: Meets the requirements

3 ASSAY

3.1 Procedure

Buffer: 1.16 g/L of d-10-camphorsulfonic acid in 0.1 M sodium acetate. Adjust with 0.1 N sodium hydroxide to a pH of 6.2.

Mobile phase: Acetonitrile, methanol, and Buffer (25:25:50)

System suitability solution: 12 µg/mL each of USP Diltiazem Hydrochloride RS and USP Desacetyl Diltiazem Hydrochloride RS in methanol

Standard solution: 1.2 mg/mL of USP Diltiazem Hydrochloride RS in methanol

Sample solution: 1.2 mg/mL of Diltiazem Hydrochloride in methanol

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 240 nm
• Column: 3.9-mm × 30-cm; packing L1
• Flow rate: 1.6 mL/min
• Injection volume: 10 µL

System suitability

• Samples: System suitability solution and Standard 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% determined from replicate injections, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of diltiazem hydrochloride (C₂₂H₂₆N₂O₄S · HCl) in the portion of sample 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 = concentration of Diltiazem Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.1%

4.2 Organic Impurities

Buffer, Mobile phase, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: Use the System suitability solution prepared as directed in the Assay.

System suitability: Proceed as directed in the Assay, except for the following:

• Sample: Standard solution
• Suitability requirements
• Relative standard deviation: NMT 10.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of desacetyl diltiazem hydrochloride in the portion of Diltiazem Hydrochloride 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 (mg/mL)

Cᵤ = concentration of Diltiazem Hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of each impurity peak, other than the main peak and the desacetyl diltiazem peak:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = response of each impurity peak 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 (mg/mL)

Cᵤ = concentration of Diltiazem Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: NMT 0.5% of desacetyl diltiazem hydrochloride; NMT 0.5% of each individual impurity; and NMT 1.0% total impurities, including desacetyl diltiazem hydrochloride

5 SPECIFIC TESTS

5.1 Optical Rotation Specific Rotation 〈781〉

Sample solution: 10 mg/mL in water

Acceptance criteria: Between +110° and +116°

5.2 Loss on Drying 〈731〉

Sample: Dry a sample at 105° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

Change to read:

USP Reference Standards 〈11〉

USP Desacetyl Diltiazem Hydrochloride RS

d-cis-3-Hydroxy-2,3-dihydro-5-[2-dimethylamino)ethyl]-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one hydrochloride.

C₂₀H₂₄N₂O₃S · HCl      408.94

USP Diltiazem Hydrochloride RS