Nicardipine Hydrochloride Injection

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

Nicardipine Hydrochloride Injection is a sterile solution of Nicardipine Hydrochloride. It contains NLT 90.0% and NMT 110.0% of the labeled amount of nicardipine hydrochloride (C₂₆H₂₉N₃O₆ · HCl).

2 IDENTIFICATION

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

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

3 ASSAY

PROCEDURE

Buffer: 1.36 g/L of monobasic potassium phosphate in water

Mobile phase: Methanol and Buffer (80:20)

Diluent: Acetonitrile and Buffer (50:50)

Standard solution: 0.1 mg/mL of USP Nicardipine Hydrochloride RS in Diluent. Sonication may be used to aid in dissolution. Pass through a suitable filter of 0.45-µm pore size. Discard the first 2-3 mL of the filtrate.

Sample solution: Nominally 0.1 mg/mL of nicardipine hydrochloride in Diluent from a suitable volume of Injection. Pass through a suitable filter of 0.45-µm pore size. Discard the first 2-3 mL of filtrate. [NOTE-The Sample solution is stable for about 26 h.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 200-400 nm.

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of nicardipine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of nicardipine hydrochloride (C₂₆H₂₉N₃O₆ · HCl) in the portion of Injection taken:

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

r_U = peak response of nicardipine from the Sample solution

r_S = peak response of nicardipine from the Standard solution

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

C_U = nominal concentration of nicardipine hydrochloride in the Sample solution (mg/mL) 

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

4.1 LIMIT OF N-BENZYL-N-METHYL-ETHANOLAMINE

Solution A: Dissolve 2.80 g of sodium perchlorate monohydrate in 1 L of water. Adjust with perchloric acid to a pH of 2.5.

Solution B: Acetonitrile and methanol (50:50)

Diluent: Acetonitrile and water (20:80)

Mobile phase: See Table 1.

Table 1

Standard solution: 2.5 µg/mL of USP N-Benzyl-N-methyl-ethanolamine RS in Diluent prepared as follows. To a suitable amount of USP N-Benzyl-N-methyl-ethanolamine RS, add Diluent to 70% of the final volume. Sonicate to dissolve. Cool, and dilute with Diluent to volume. Pass the solution through a suitable filter of 0.45-µm pore size.

Sample solution: Nominally 0.5 mg/mL of nicardipine hydrochloride in Diluent from a suitable volume of Injection. Pass the solution through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 205 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Temperatures

Autosampler: 10°

Column: 30°

Flow rate: 1.5 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of N-benzyl-N-methyl-ethanolamine in the portion of Injection taken:

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

r_U = peak response of N-benzyl-N-methyl-ethanolamine from the Sample solution

r_S = peak response of N-benzyl-N-methyl-ethanolamine from the Standard solution

C_S = concentration of USP N-Benzyl-N-methyl-ethanolamine RS in the Standard solution (mg/mL) 

C_U = nominal concentration of nicardipine hydrochloride in the Sample solution (mg/mL) 

Acceptance criteria: NMT 0.7%

4.2 ORGANIC IMPURITIES

Solution A: 3.5 g/L of sodium perchlorate monohydrate in water. Add 1 mL/L of triethylamine, and adjust with perchloric acid to a pH of 2.0.

Solution B: Acetonitrile and methanol (70:30)

Mobile phase: See Table 2.

Table 2

Standard solution: 0.02 mg/mL of USP Nicardipine Hydrochloride RS in methanol prepared as follows. To a suitable amount of USP Nicardipine Hydrochloride RS add methanol to 60% of the final volume. Sonicate to dissolve, Cool, and dilute with methanol to volume. Pass the solution through a suitable filter of 0.45-µm pore size.

Sensitivity solution: 0.002 mg/mL of USP Nicardipine Hydrochloride RS in methanol from Standard solution

Sample solution: Nominally 2 mg/mL of nicardipine hydrochloride in methanol from a suitable volume of Injection. Pass the solution through a suitable filter of 0.45-µm pore size. [NOTE-The Sample solution is stable for about 42 h at 10°.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 239 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Temperatures

Autosampler: 10°

Column: 50°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Samples: Standard solution and Sensitivity solution

Suitability requirements

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified impurity and any unspecified degradation product in the portion of Injection taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (1/F) x 100

r_U = peak response of each specified impurity or any unspecified degradation product from the Sample solution

r_S = peak response of nicardipine from the Standard solution

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

C_U = nominal concentration of nicardipine hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3.

Table 3

^a 5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid.

^b 3-(2-[Benzyl(methyl)amino]ethyl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate.

^c Total impurities include the sum of all organic impurities and N-benzyl-N-methyl-ethanolamine.

5 OTHER COMPONENTS

CONTENT OF SORBITOL (if present)

Buffer: 1 g/L of tetrabutylammonium hydrogen sulfate in water

Mobile phase: Acetonitrile and Buffer (70:30)

Standard solution: 4.8 mg/mL of USP Sorbitol RS in Mobile phase. Pass the solution through a suitable filter of 0.45-µm pore size. Sonication may be necessary to aid in dissolution.

Sample solution: Nominally 4.8 mg/mL of sorbitol in Mobile phase from the contents of NLT 3 Injection vials. Pass the solution through a suitable filter of 0.45-µm pore size. [NOTE-Sample solution is stable for about 24 h.]

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: Refractive index

Column: 4.6-mm x 25-cm; 5-µm packing L8

Temperatures

Column: 40°

Detector: 50°

Flow rate: 1 mL/min

Injection volume: 25 µL

Run time: NLT 2 times the retention time of sorbitol

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of sorbitol (C₆H₁₄O₆) in the portion of Injection taken:

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

r_U = peak response of sorbitol from the Sample solution

r_S = peak response of sorbitol from the Standard solution 

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

C_U = nominal concentration of sorbitol in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

6 SPECIFIC TESTS

BACTERIAL ENDOTOXINS TEST (85): Meets the requirements

STERILITY TESTS (71): Meets the requirements

PH (791): 3.0-4.2

PARTICULATE MATTER IN INJECTIONS (788): Meets the requirements for small-volume injections

OTHER REQUIREMENTS: Meets the requirements for Injections and Implanted Drug Products (1)

7 ADDITIONAL REQUIREMENTS

Change to read:

PACKAGING AND STORAGE: Preserve in single-dose glass vials. Protect from light. (RB 1-Feb-2025) Store at controlled room temperature.

LABELING: Label it to indicate that it is to be diluted to the appropriate strength with a suitable intravenous fluid prior to administration. table intn

USP REFERENCE STANDARDS (11)

USP N-Benzyl-N-methyl-ethanolamine RS

2-[Benzyl(methyl)amino]ethanol.

C₁₀H₁₅NO            165.23

USP Nicardipine Hydrochloride RS

USP Sorbitol RS

D-Glucitol.

C₆H₁₄O₆            182.17