Cyproheptadine Hydrochloride Oral Solution

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

Cyproheptadine Hydrochloride Oral Solution contains NLT 90.0% and  NMT 110.0% of the labeled amount of cyproheptadine hydrochloride (C₂₁H₂₁N · 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

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: Nominally 40 µg/mL of cyproheptadine hydrochloride from Oral Solution in Diluent prepared as follows. Transfer an appropriate volume of Oral Solution to a suitable volumetric flask and dilute with Diluent to volume.

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 266 nm. For Identification B, use a diode array detector in the range of 210-400 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 1.0%

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of cyproheptadine hydrochloride (C₂₁H₂₁N · HCl) in the portion of Oral Solution taken:

                 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

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

C_U = nominal concentration of cyproheptadine hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

Change to read:

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: 0.6 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,

(ERR 1-Jan-2020)

Sample solution: Oral Solution

4.1.1 System suitability

Sample: Standard solution

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

Suitability requirements

Resolution: NLT 3.0 between amitriptyline related compound A and cyproheptadine related compound A

Relative standard deviation: NMT 5.0% for cyproheptadine

4.1.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual unspecified degradation product in the portion of Oral Solution taken:

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

r_U = peak response of any individual unspecified degradation product 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_U = nominal concentration of cyproheptadine hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.10%.

Table 2

^a Process impurity included in the table for identification only. Process impurities are controlled in the drug substance and are not to be reported or included in the total impurities for the drug product.

5 SPECIFIC TESTS

pH 〈791〉: 3.5–4.5

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at controlled room temperature.

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