Cyclobenzaprine 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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1 DEFINITION

Cyclobenzaprine Hydrochloride contains NLT 98.0% and NMT 102.0% of cyclobenzaprine hydrochloride (C₂₀H₂₁N . HCI), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M (CN 1-May-2020)

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: 20 mg/mL of Cyclobenzaprine Hydrochloride in water

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 PROCEDURE

Mobile phase: Dissolve 2.0 g of ammonium acetate in 350 mL of water. Add 650 mL of methanol, and adjust with 25% ammonium hydroxide to a pH of 8.9.

Standard solution: 0.2 mg/mL of USP Cyclobenzaprine Hydrochloride RS in Mobile phase

Sample solution: 0.2 mg/mL of Cyclobenzaprine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm x 15-cm; 5-µm packing 11

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of cyclobenzaprine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of cyclobenzaprine hydrochloride (C₂₀H₂₁N . HCI) in the portion of Cyclobenzaprine Hydrochloride taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution 

C_s = concentration of USP Cyclobenzaprine Hydrochloride RS in the Standard solution (mg/mL)

C_u = concentration of Cyclobenzaprine 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%

Change to read:

4.2 ORGANIC IMPURITIES

Buffer: 5.7 g/L of ammonium acetate in water. Adjust with 25% ammonium hydroxide to a pH of 7.2.

Mobile phase: Methanol and Buffer (65:35)

System suitability solution: 0.5 mg/mL of USP Cyclobenzaprine Hydrochloride RS and 0.75 µg/mL each of USP Cyclobenzaprine Related Compound A RS and USP Cyclobenzaprine Related Compound B RS in Mobile phase

Standard solution: 0.5 µg/mL of USP Cyclobenzaprine Hydrochloride RS in Mobile phase

Sample solution: 500 µg/mL of Cyclobenzaprine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm x 25-cm; 5-µm packing 17

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 3.5 times the retention time of cyclobenzaprine

System suitability

Samples: System suitability solution, and Standard solution

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

Suitability requirements

Resolution: NLT 1.5 between cyclobenzaprine related compound A and cyclobenzaprine related compound B, System suitability solution

Tailing factor: NMT 2.0 for the cyclobenzaprine peak, System suitability solution

Relative standard deviation: NMT 5.0% for cyclobenzaprine, Standard solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each specified impurity and any individual unspecified impurity in the portion of Cyclobenzaprine Hydrochloride taken:

Result = (r_u/r_s) × (C_s/C_u) × 100 × (1/F) × 100

r_u = peak response of each impurity from the Sample solution 

r_s = peak response of cyclobenzaprine from the Standard solution 

C_s = concentration of USP Cyclobenzaprine Hydrochloride RS in the Standard solution (µg/mL)

C_u = concentration of Cyclobenzaprine Hydrochloride in the Sample solution (µg/mL)

F = relative response factor for each impurity (see Table 1) 

Acceptance criteria: See Table 1.

Table 1

a 3-(5H-Dibenzo[a,d)cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine N-oxide.

b 5H-Dibenzo[a,d)cycloheptene-5-ol.

c 10,11-Dihydro-N,N-dimethyl-5H-dibenzo[a,d]cycloheptene-45.Y, -propylamine.

d Dibenzo[a,d]cyclohepten-5-one.

5 SPECIFIC TESTS

5.1 LOSS ON DRYING (731)

Analysis: Dry at 105° to constant weight.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE: Preserve in well-closed containers.

6.2 USP REFERENCE STANDARDS (11)

USP Cyclobenzaprine Hydrochloride RS

USP Cyclobenzaprine Related Compound A RS

5-[3-(Dimethylamino)propyl]-5H-dibenzo[a,d]-cyclohepten-5-ol.

C₂₀H₂₃NO       293.40

USP Cyclobenzaprine Related Compound B RS

3-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine hydrochloride.

C₁₉H₁₉N . HCI       297.82