Terbinafine Tablets
DEFINITION
Terbinafine Tablets contain Terbinafine Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of terbinafine (C21H25N).
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
0.85 g/L of monobasic potassium phosphate in water. Add 1 g of sodium 1-decanesulfonate, and adjust with dilute phosphoric acid to a pH of 3.0.
Mobile phase:
Acetonitrile and Buffer (2:3)
Standard solution:
0.2 mg/mL of USP Terbinafine Hydrochloride RS in Mobile phase (equivalent to 0.19 mg/mL of terbinafine)
Sample stock solution:
0.5 mg/mL of terbinafine in Mobile phase, from crushed, finely powdered Tablets. [Note—Sonicate for 20 min with intermittent shaking. ]
Sample solution:
0.2 mg/mL of terbinafine in Mobile phase, from Sample stock solution
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
3.9-mm × 15-cm; 5-µm packing L7
Flow rate:
1.8 mL/min
Injection size:
5 µL
Run time:
1.5 times the retention time of the terbinafine peak
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C21H25N in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Terbinafine Hydrochloride RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of terbinafine in the Sample solution (µg/mL) |
| Mr1 | = | = molecular weight of terbinafine, 291.44 |
| Mr2 | = | = molecular weight of terbinafine hydrochloride, 327.90 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
pH 3.0 Citrate buffer (dissolve 21.0 g of citric acid in 200 mL of 1 N sodium hydroxide, and dilute with water to 1000 mL. Dilute 40.3 mL of this solution with 0.1 M hydrochloric acid to 100 mL); 500 mL
Apparatus 2:
50 rpm
Time:
30 min
Standard solution:
32 µg/mL of USP Terbinafine Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable 0.45-µm filter. Dilute with Medium, if necessary.
Spectrometric conditions
Mode:
UV
Analytical wavelength:
283 nm
Cell length:
1 cm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of C21H25N dissolved:
Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × D × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of terbinafine hydrochloride in the Standard solution (mg/mL) |
| L | = | = Tablet label claim of terbinafine (mg) |
| Mr1 | = | = molecular weight of terbinafine, 291.44 |
| Mr2 | = | = molecular weight of terbinafine hydrochloride, 327.90 |
| V | = | = volume of Medium, 500 mL |
| D | = | = dilution factor |
Tolerances:
NLT 80% (Q) of the labeled amount of C21H25N is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure 1
Buffer and Mobile phase:
Proceed as directed in the Assay.
Standard solution:
0.7 µg/mL of USP Terbinafine Hydrochloride RS in Mobile phase (equivalent to 0.6 µg/mL of terbinafine)
Sample solution:
Proceed as directed in the Assay.
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
3.9-mm × 15-cm; 5-µm packing L7
Flow rate:
1.8 mL/min
Injection size:
50 µL
Run time:
4 times the retention time of the terbinafine peak
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 10.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of any other unspecified degradation product in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × (Mr1/Mr2) × 100
| rU | = | = peak response of each individual impurity 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 | = | = nominal concentration of terbinafine in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
| Mr1 | = | = molecular weight of terbinafine, 291.44 |
| Mr2 | = | = molecular weight of terbinafine hydrochloride, 327.90 |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.7%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| N-Methyl-1-(naphthalen-1-yl) methanamine | 0.14 | 1.5 | 0.2 |
| Terbinafine | 1.0 | — | — |
| Any single unspecified degradation product | — | 1.0 | 0.1 |
• Procedure 2: Limit of Terbinafine Dimer
Diluent:
Acetonitrile and water (4:1)
Solution A:
1 mL/L of triethyl amine in water
Solution B:
1 mL of triethyl amine in a mixture of acetonitrile and water (19:1)
Mobile phase:
See the gradient table below.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 40 | 60 |
| 8 | 30 | 70 |
| 18 | 30 | 70 |
| 24 | 16 | 84 |
| 26 | 5 | 95 |
| 30 | 0 | 100 |
| 37 | 40 | 60 |
| 45 | 40 | 60 |
Standard solution:
1.4 µg/mL of USP Terbinafine Hydrochloride RS in Diluent (equivalent to 1.2 µg/mL of terbinafine)
Sample solution:
2.5 mg/mL of terbinafine in Diluent, from crushed, finely powdered Tablets. [Note—Sonicate for 20 min with intermittent shaking. ]
Chromatographic system
Mode:
LC
Detector:
UV 280 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1 mL/min
Temperature:
52
Injection size:
100 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 10.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the terbinafine dimer in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × (Mr1/Mr2) × 100
| rU | = | = peak response of the terbinafine dimer in 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 | = | = nominal concentration of terbinafine in the Sample solution (mg/mL) |
| F | = | = relative response factor for the terbinafine dimer |
| Mr1 | = | = molecular weight of terbinafine, 291.44 |
| Mr2 | = | = molecular weight of terbinafine hydrochloride, 327.90 |
Acceptance criteria:
See Impurity Table 2.
Impurity Table 2
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Terbinafine | 1.0 | — | — |
| Terbinafine dimera | 2.0 | 2.1 | 0.05 |
|
a
(2E,4E)-4-(4,4-Dimethylpent-2-ynylidene)-N1,N5-dimethyl-N1,N5-bis(naphthalen-1-ylmethyl)pent-2-ene-1,5-diamine.
|
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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 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4790
Pharmacopeial Forum: Volume No. 37(3)