Terbinafine Hydrochloride
C21H25N·HCl 327.90
1-Naphthalenemethanamine, N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-, (E)-, hydrochloride;
(E)-N-(6,6-Dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethylamine, hydrochloride;
(2E)-N,6,6-Trimethyl-N-(naphthalen-1-ylmethyl)hept-2-en-4-yn-1-amine hydrochloride
[78628-80-5].
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C21H25N·HCl 327.90
1-Naphthalenemethanamine, N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-, (E)-, hydrochloride;
(E)-N-(6,6-Dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethylamine, hydrochloride;
(2E)-N,6,6-Trimethyl-N-(naphthalen-1-ylmethyl)hept-2-en-4-yn-1-amine hydrochloride
[78628-80-5].DEFINITION
Terbinafine Hydrochloride contains NLT 98.0% and NMT 102.0% of C21H25N·HCl, calculated on the dried basis.
IDENTIFICATION
• B. Identification Tests—General, Chloride 
191
:
Meets the requirements of the test when using dehydrated alcohol as a solvent.
191:
Meets the requirements of the test when using dehydrated alcohol as a solvent.
ASSAY
• Procedure
[Note—Protect all solutions containing Terbinafine Hydrochloride from light. ]
Buffer, Solution A, Solution B, Solution C, Mobile phase, Diluent, and Chromatographic system:
Proceed as directed in the test for Organic Impurities.
Standard solution:
0.5 mg/mL of USP Terbinafine Hydrochloride RS in Diluent
System suitability solution:
1 mg/mL of USP Terbinafine Hydrochloride RS in Diluent. Expose to UV light at 254 nm for 1 h.
Sample solution:
0.5 mg/mL of Terbinafine Hydrochloride in Diluent
System suitability
Samples:
Standard solution and System suitability solution
[Note—The relative retention times for cis-terbinafine and terbinafine are 0.94 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between cis-terbinafine 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 C21H25N·HCl in the portion of Terbinafine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of terbinafine from the Sample solution |
| rS | = | = peak response of terbinafine from the Standard solution |
| CS | = | = concentration of USP Terbinafine Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = concentration of Terbinafine Hydrochloride in the Sample solution (mg/mL) |
Acceptance criteria:
98.0%–102.0% on the dried basis
IMPURITIES
Inorganic Impurities
• Residue on Ignition 281:
NMT 0.1%
281:
NMT 0.1%
Organic Impurities
• Procedure
[Note—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 the gradient table below.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 100 | 0 |
| 4 | 100 | 0 |
| 25 | 0 | 100 |
| 30 | 0 | 100 |
| 30.1 | 100 | 0 |
| 38 | 100 | 0 |
Diluent:
Acetonitrile and water (1:1)
Standard solution:
0.5 µg/mL of USP Terbinafine Hydrochloride RS in Diluent
Sample solution:
0.5 mg/mL of Terbinafine Hydrochloride in Diluent
System suitability solution:
1 mg/mL of USP Terbinafine Hydrochloride RS in Diluent. Expose to UV light at 254 nm for 1 h.
Sensitivity solution:
0.25 µg/mL of terbinafine hydrochloride in Diluent from the Standard solution
Chromatographic system
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 size:
20 µL
System suitability
Samples:
Standard solution, System suitability solution, and Sensitivity solution
Suitability requirements
Resolution:
NLT 2.0 between cis-terbinafine and terbinafine, System suitability solution
Relative standard deviation:
NMT 10%, Standard solution
Signal-to-noise ratio:
NLT 10, 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 Impurity Table 1.
Calculate the percentage of each impurity in the portion of Terbinafine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of the terbinafine peak from the Standard solution |
| CS | = | = concentration of USP Terbinafine Hydrochloride RS in the Standard solution (µg/mL) |
| CU | = | = concentration of Terbinafine Hydrochloride in the Sample solution (µg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
[Note—Disregard any peak observed in the blank, and any peak less than 0.05%. ]
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| N-Methyl-C-(naphthalen-1-yl)methanamine | 0.1 | 1.7 | 0.1 |
| trans-Isoterbinafinea | 0.92 | 1.0 | 0.1 |
| cis-Terbinafineb | 0.94 | 1.0 | 0.1 |
| Terbinafine | 1.0 | — | — |
| 4-Methylterbinafinec | 1.1 | 1.0 | 0.1 |
| Terbinafine dimerd | 1.7 | 2.5 | 0.05 |
| Any other individual impurity | — | 1.0 | 0.1 |
|
a
(2E)-N,6,6-Trimethyl-N-(naphthalen-2-ylmethyl)hept-2-en-4-yn-1-amine.
b
(2Z)-N,6,6-Trimethyl-N-(naphthalen-1-ylmethyl)hept-2-en-4-yn-1-amine.
c
(2E)-N,6,6-Trimethyl-N-[(4-methylnaphthalen-1-yl)methyl]hept-2-en-4-yn-1-amine.
d
(2E,4E)-4-(4,4-Dimethylpent-2-ynylidene)-N1,N5-dimethyl-N1,N5-bis(naphthalen-1-ylmethyl)pent-2-ene-1,5-diamine.
|
|||
SPECIFIC TESTS
• Loss on Drying 731:
Dry a sample at 105 to constant weight: it loses NMT 0.5% of its weight.
731:
Dry a sample at 105 to constant weight: it loses NMT 0.5% of its weight.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, protected from light. Store at room temperature.
• USP Reference Standards 11
11
USP Terbinafine Hydrochloride RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Leonel M. Santos, Ph.D.
Senior Scientific Liaison 1-301-816-8168 |
(SM12010) Monographs - Small Molecules 1 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4789
Pharmacopeial Forum: Volume No. 35(6) Page 1480