Terbinafine 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

Terbinafine Hydrochloride contains NLT 98.0% and NMT 102.0% of terbinafine hydrochloride (C₂₁H₂₅N · HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

B. IDENTIFICATION TESTS—GENERAL, Chloride 〈191〉: Meets the requirements of the test when using dehydrated alcohol as a solvent

3 ASSAY

PROCEDURE

Protect all solutions containing Terbinafine Hydrochloride from light.

Buffer: Prepare a solution in water containing 2.0 mL/L of triethylamine. Adjust with diluted acetic acid to a pH of 7.5.

Solution A: Solution C and Buffer (7:3)

Solution B: Solution C and Buffer (95:5) Solution C: Methanol and acetonitrile (3:2)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (1:1)

System suitability solution: 1 mg/mL of USP Terbinafine Hy drochloride RS and 5 µg/mL of USP Terbinafine Related Compound B RS in Diluent

Standard solution: 0.5 mg/mL of USP Terbinafine Hydrochloride RS in Diluent Sample solution: 0.5 mg/mL of Terbinafine Hydrochloride in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 3.0-mm × 15-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 0.8 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE—The relative retention times for terbinafine related compound B and terbinafine are 0.94 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between terbinafine related compound B and terbinafine, System suitability solution Tailing factor: NLT 0.8 and NMT 1.5 for terbinafine, Standard solution

Relative standard deviation: NMT 2.0% for terbinafine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of terbinafine hydrochloride (C₂₁H₂₅N · HCl) in the portion of Terbinafine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of terbinafine from the Sample solution

r_S = peak response of terbinafine from the Standard solution

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

C_U = concentration of Terbinafine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION 〈281〉: NMT 0.1%

ORGANIC IMPURITIES

Protect all solutions containing Terbinafine Hydrochloride from light.

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

Standard solution: 0.5 µg/mL each of USP Terbinafine Hydrochloride RS, USP Terbinafine Related Compound A RS, USP Terbinafine Related Compound B RS, USP Terbinafine Related Compound C RS, and USP Terbinafine Related Compound D RS in Diluent

Sample solution: 0.5 mg/mL of Terbinafine Hydrochloride in Diluent

Sensitivity solution: 0.25 µg/mL of USP Terbinafine Hydrochloride RS in Diluent from the Standard solution System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution Suitability requirements

Resolution: NLT 2.0 between terbinafine related compound B and terbinafine, System suitability solution Relative standard deviation: NMT 10% for terbinafine, Standard solution

Signal-to-noise ratio: NLT 10 for terbinafine, Sensitivity solution Calculate the signal-to-noise ratio:

Result = (2H)/h

H = measured height of the terbinafine peak

h = amplitude of the average measured baseline noise

Analysis

Samples: Standard solution and Sample solution

Identify the peaks based on their relative retention times as given in Table 2.

Calculate the percentage of terbinafine related compound A, terbinafine related compound B, terbinafine related compound C, and terbinafine related compound D in the portion of Terbinafine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of terbinafine related compound A, terbinafine related compound B, terbinafine related compound C, or terbinafine related compound D from the Sample solution

r_S = peak response of terbinafine related compound A, terbinafine related compound B, terbinafine related compound C, or terbinafine related compound D from the Standard solution

C_S = concentration of USP Terbinafine Related Compound A RS, USP Terbinafine Related Compound B RS, USP Terbinafine Related Compound C RS, or USP Terbinafine Related Compound D RS in the Standard solution (µg/mL)

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

Calculate the percentage of terbinafine dimer or any other individual impurity in the portion of Terbinafine Hydrochloride taken:

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

r_U = peak response of terbinafine dimer or any other individual impurity from the Sample solution

r_S = peak response of the terbinafine peak from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard any peak observed in the blank, and any peak less than 0.05%.

Table 2

^a  N-Methyl-1-(naphthalen-1-yl)methanamine, also known as N-methyl-C-(naphthalen-1-yl)methanamine.

^b   trans-Isoterbinafine or (2E)-N,6,6-Trimethyl-N-(naphthalen-2-ylmethyl)hept-2-en-4-yn-1-amine.

^c cis-Terbinafine or (2Z)-N,6,6-Trimethyl-N-(naphthalen-1-ylmethyl)hept-2-en-4-yn-1-amine.

^d  4-Methylterbinafine or (2E)-N,6,6-Trimethyl-N-((4-methylnaphthalen-1-yl)methyl)hept-2-en-4-yn-1-amine.

^e (2E,4E)-4-(4,4-Dimethylpent-2-ynylidene)-N1,N5-dimethyl-N1,N5-bis(naphthalen-1-ylmethyl)pent-2-ene-1,5-diamine.

5 SPECIFIC TESTS

LOSS ON DRYING 〈731〉

Analysis: Dry at 105° to constant weight. Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS 〈11〉

USP Terbinafine Hydrochloride RS

USP Terbinafine Related Compound A RS

N-Methyl-C-(naphthalen-1-yl)methanamine hydrochloride. C₁₂H₁₃N · HCl    207.70

USP Terbinafine Related Compound B RS

(2Z)-N,6,6-Trimethyl-N-(naphthalen-1-ylmethyl)hept-2-en-4-yn-1-amine hydrochloride. C₂₁H₂₅N · HCl    327.89

USP Terbinafine Related Compound C RS

(2E)-N,6,6-Trimethyl-N-(naphthalen-2-ylmethyl)hept-2-en-4-yn-1-amine hydrochloride. C₂₁H₂₅N · HCl    327.89

USP Terbinafine Related Compound D RS

(2E)-N,6,6-Trimethyl-N-[(4-methylnaphthalen-1-yl)methyl]hept-2-en-4-yn-1-amine hydrochloride. C₂₂H₂₇N · HCl    341.92