Cyproheptadine 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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C₂₁H₂₁N · HCI · 1⁄2H₂O                 350.88

C₂₁H₂₁N · HCI                  323.87

Piperidine, 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-methyl-, hydrochloride, sesquihydrate;

4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-methylpiperidine hydrochloride sesquihydrate CAS RN^®: 41354-29-4; UNII: NJ82J0F8QC.

Anhydrous CAS RN: 969-33-5; UNII: OS9323MCT0.

1 DEFINITION

Cyproheptadine Hydrochloride contains NLT 98.0% and NMT 102.0% of cyproheptadine hydrochloride (C₂₁H₂₁N · HCI), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197KA _{▲(CN 1-MAY-2020)}

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

3 ASSAY

3.1 PROCEDURE

Solution A: 1 mL/L of trifluoroacetic acid in water

Solution B: Acetonitrile and Solution A (38:62)

Solution C: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (38:62)

Standard solution: 40 μg/mL of USP Cyproheptadine Hydrochloride RS in Diluent. Sonication may be used to aid dissolution.

Sample solution: 40 μg/mL of Cyproheptadine Hydrochloride in Diluent. Sonication may be used to aid dissolution.

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 266 nm

Column: 4.6-mm x 15-cm; 2.7-µm packing 160

Flow rate: 1 mL/min

Injection volume: 15 µL

3.1.2 System suitability

Sample: Standard solution

3.1.3 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of cyproheptadine hydrochloride (C₂₁H₂₁N · HCI) in the portion of Cyproheptadine Hydrochloride taken: 21

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution s

C_S = concentration of USP Cyproheptadine Hydrochloride RS in the Standard solution (µg/mL)

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

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

4.1 ORGANIC IMPURITIES

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

Standard stock solution: 50 µg/mL each of USP Cyproheptadine Hydrochloride RS. USP Cyproheptadine Related Compound A RS, USP Amitriptyline Related Compound A RS, and USP Cyproheptadine Related Compound C RS, prepared as follows. Transfer a suitable quantity of each Reference Standard to an appropriate volumetric flask. Add 38% of the total flask volume of acetonitrile to dissolve, and then dilute with water to volume.

Standard solution: 0.75 µg/mL each of USP Cyproheptadine Hydrochloride RS, USP Cyproheptadine Related Compound A RS, USP Amitriptyline Related Compound A RS, and USP Cyproheptadine Related Compound C RS from the Standard stock solution in Diluent

Sensitivity solution: 0.25 µg/mL each of USP Cyproheptadine Hydrochloride RS, USP Cyproheptadine Related Compound A RS, USP Amitriptyline Related Compound A RS, and USP Cyproheptadine Related Compound C RS from the Standard stock solution in Diluent

Sample solution: 500 µg/mL of Cyproheptadine Hydrochloride in Diluent. Sonication may be used to aid dissolution.

4.2 System suitability

Samples: Standard solution and Sensitivity solution

[NOTE-See Table 2 for the relative retention times.]

4.3 Suitability requirements

Resolution: NLT 3.0 between amitriptyline related compound A and cyproheptadine related compound A, Standard solution

Relative standard deviation: NMT 5.0% for cyproheptadine, cyproheptadine related compound A, amitriptyline related compound A, and cyproheptadine related compound C, Standard solution

Signal-to-noise ratio: NLT 10 for cyproheptadine hydrochloride, Sensitivity solution

4.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of cyproheptadine related compound A, amitriptyline related compound A, and cyproheptadine related compound C in the portion of Cyproheptadine Hydrochloride taken:

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

r_U = peak response of each related compound from the Sample solution

r_S = peak response of each related compound from the Standard solution

C_S = concentration of the appropriate USP Reference Standard in the Standard solution (µg/mL)

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

Calculate the percentage of any individual unknown impurity in the portion of Cyproheptadine Hydrochloride taken:

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

r_U = peak response of any individual unknown impurity from the Sample solution

r_S = peak response of cyproheptadine hydrochloride from the Standard solution S

C_S = concentration of USP Cyproheptadine Hydrochloride RS in the Standard solution (µg/mL) C_{5} = 1

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

Acceptance criteria: See Table 2. Disregard any peak less than 0.05%.

Table 2

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method /: 7.0%-9.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS (11)

USP Amitriptyline Related Compound A RS

Dibenzosuberone.

C₁₅H₁₂O              208.26

USP Cyproheptadine Hydrochloride RS

USP Cyproheptadine Related Compound A RS

5H-Dibenzo[a,d]cycloheptene.

C₁₅H₁₂               192.26

USP Cyproheptadine Related Compound C RS

5-(1-Methyl-piperidin-4-yl)-5H-dibenzo[a,d]cyclohepten-5-ol.

C₂₁H₂₃NO            305.41