Nicardipine 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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C₂₆H₂₉N₃O₆ · HCl           515.99

3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, methyl 2-(methyl (phenylmethyl)amino]ethyl ester, monohydrochloride;

2-(Benzylmethylamino) ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate monohydrochloride CAS RN^®: 54527-84-3; UNII: K5BC5011K3.

Nicardipine free base

C₂₆H₂₉N₃O₆ · HCl              479.53 CAS RN: 55985-32-5; UNII: CZ5312222S.

1 DEFINITION

Nicardipine Hydrochloride contains NLT 98.0% and NMT 102.0% of nicardipine hydrochloride (C₂₆H₂₉N₃O₆ · HCl), calculated on the dried basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K or 197A

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 ( 191), Chemical Identification Tests, Chloride

Sample solution: 2.5 mg/ml. in methanol

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Protect all solutions from light.

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Adjust the solution with potassium hydroxide to a pH of 4.8.

Solution A: Acetonitrile and methanol (90:10)

Mobile phase: Solution A and Buffer (38:62)

System suitability solution: 0.02 mg/mL each of USP Nicardipine Hydrochloride RS, USP Nicardipine Related Compound B RS, USP Nicardipine Related Compound C RS, and USP Nicardipine Related Compound D RS in Mobile phase

Standard solution: 0.1 mg/mL of USP Nicardipine Hydrochloride RS in Mobile phase

Sample solution: 0.1 mg/mL of Nicardipine Hydrochloride in Mobile phase. [NOTE-Sonication may be necessary for complete dissolution.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 237 nm

Column: 4.6-mm x 25-cm; 4-µm packing L7

Column temperature: 35°

Flow rate: 1.2 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of the nicardipine peak

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for nicardipine, nicardipine related compound D, nicardipine related compound C, and nicardipine related compound B are 1.00, 1.10, 1.43, and 1.93 respectively.]

Suitability requirements

Resolution: NLT 1.5 between nicardipine and nicardipine related compound D, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of nicardipine hydrochloride (C₂₆H₂₉N₃O₆ · HCl) in the portion of Nicardipine Hydrochloride taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of nicardipine from the Sample solution

r_S = speak response of nicardipine from the Standard solution

C_S = concentration of USP Nicardipine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Nicardipine 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

Protect all solutions from light.

Buffer, Solution A, Mobile phase, and System suitability solution: Prepare as directed in the Assay.

Standard solution 1: 3 µg/mL of USP Nicardipine Hydrochloride RS in Mobile phase

Standard solution 2: 0.6 µg/mL of USP Nicardipine Related Compound B RS in Mobile phase

Sensitivity solution: 0.3 µg/mL of USP Nicardipine Hydrochloride RS from Standard solution 1 in Mobile phase

Sample solution: 0.6 mg/mL of Nicardipine Hydrochloride in Mobile phase. [NOTE-Sonication may be necessary for complete dissolution.]

Chromatographic system: Proceed as directed in the Assay, except for the Run time.

Run time: NLT 4 times the retention time of nicardipine

System suitability

Samples: System suitability solution, Standard solution 1, Standard solution 2, and Sensitivity solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between nicardipine and nicardipine related compound D; NLT 1.5 between nicardipine related compound D and nicardipine related compound C, System suitability solution

Relative standard deviation: NMT 2%, Standard solution 1 and Standard solution 2

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution 1, Standard solution 2, and Sample solution

Calculate the percentage of nicardipine related compound B in the portion of Nicardipine Hydrochloride taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of nicardipine related compound B from the Sample solution

r_S = peak response of nicardipine related compound B from Standard solution 2

C_S = concentration of USP Nicardipine Related Compound B. RS in Standard solution 2 (µg/mL)

C_U = concentration of Nicardipine Hydrochloride in the Sample solution (µg/mL)

Calculate the percentage of nicardipine related compound C and nicardipine related compound D or any unspecified impurity in the portion of Nicardipine Hydrochloride taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each specified and unspecified impurity from the Sample solution

r_S = peak response of nicardipine from Standard solution 1

C_S = concentration of USP Nicardipine Hydrochloride RS in Standard solution 1 (µg/mL) 

C_U = concentration of Nicardipine Hydrochloride in the Sample solution (µg/mL) 

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

5 SPECIFIC TESTS

LOSS ON DRYING (731).

Analysis: Dry at 105", protected from light, to constant weight.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tightly closed containers, protected from light. Store at room temperature.

Change to read:

USP REFERENCE STANDARDS (11)

USP Nicardipine Hydrochloride RS

USP Nicardipine Related Compound B RS

^▲3-(2-[Benzyl (methyl)amino]ethyl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate oxalate. _{▲(ERR 1-Aug-2024)}

C₂₆H₂₉N₃O₆ · C₂H₂O₄         567.55

USP Nicardipine Related Compound C RS

Dimethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

C₁₇H₁₈N₂O₆           346.34

USP Nicardipine Related Compound D RS

Bis(2-[benzyl (methyl)amino]ethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride. (ERR 1-Aug-2024)

C₃₅H₄₀N₄O₆ · 2HCl          685.64