Tramadol Hydrochloride Tablets
711
DEFINITION
Tramadol Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of tramadol hydrochloride (C16H25NO2·HCl).
IDENTIFICATION
• A. Infrared Absorption 197K
197K
Sample solution:
Transfer powdered Tablets, equivalent to 200 mg of tramadol hydrochloride, into a 50-mL volumetric flask, add 20 mL of dichloromethane, and sonicate. Filter, and transfer the clear supernatant to a separating funnel. Extract the dichloromethane layer with two 10-mL portions of 2 N sodium hydroxide, and discard the aqueous layer. Dry the dichloromethane layer over anhydrous sodium sulfate, and filter. Evaporate this solution to dryness under a stream of nitrogen.
Acceptance criteria:
Meet the requirements
• B.
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
Solution A:
Dissolve 5 mL of perchloric acid in 950 mL of water in a 1-L volumetric flask. Add 4 mL of 25% ammonia water, dilute with water to volume, and mix. Adjust with 25% ammonia water to a pH of 2.2 ± 0.2.
Mobile phase:
Acetonitrile and Solution A (23:77)
Standard solution:
0.1 mg/mL of USP Tramadol Hydrochloride RS in 0.1 N hydrochloric acid
Sample solution:
Finely powder NLT 20 Tablets. Transfer a portion of the powder, equivalent to 50 mg of tramadol hydrochloride, into a 100-mL volumetric flask. Add 70 mL of 0.1 N hydrochloric acid, sonicate for 5 min, and shake for 10 min. Dilute with 0.1 N hydrochloric acid to volume, and mix. Pass a portion of this solution through a suitable filter, discarding the first 20 mL of the filtrate. Transfer 10 mL of the clear filtrate into a 50-mL volumetric flask, dilute with 0.1 N hydrochloric acid to volume, and mix.
Chromatographic system
Mode:
LC
Detector:
UV 273 nm
Column:
3.9-mm × 15-cm; packing L7
Flow rate:
2 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of tramadol hydrochloride (C16H25NO2·HCl) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Tramadol Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of tramadol hydrochloride in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
Change to read:
• Dissolution 711
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 1:
100 rpm
Time:
30 min
Solution A, Mobile phase, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Standard solution:
0.055 mg/mL of USP Tramadol Hydrochloride RS in Medium
Sample solution:
Withdraw 9 mL from the dissolution vessel, and pass through a 
suitableUSP35 filter. Discard the first 3 mL of the filtrate.
suitableUSP35 filter. Discard the first 3 mL of the filtrate.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of tramadol hydrochloride (C16H25NO2·HCl) dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Tramadol Hydrochloride RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of tramadol hydrochloride (C16H25NO2·HCl) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
Procedure for content uniformity
Solution A, Mobile phase, Standard solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Sample solution:
Transfer 1 whole Tablet to a 100-mL volumetric flask, add 70 mL of 0.1 N hydrochloric acid, sonicate until the Tablet is completely disintegrated, and shake for 10 min. Dilute with 0.1 N hydrochloric acid to volume, and mix. Pass a portion of this solution through a suitable filter, discarding the first 20 mL of the filtrate. Transfer 10 mL of the clear filtrate into a 50-mL volumetric flask, dilute with 0.1 N hydrochloric acid to volume, and mix.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of tramadol hydrochloride (C16H25NO2·HCl) in the Tablet taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Tramadol Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of tramadol hydrochloride in the Sample solution (mg/mL) |
IMPURITIES
Organic Impurities
• Procedure
Solution A and Mobile phase:
Prepare as directed in the Assay.
System suitability solution:
0.2 mg/mL each of USP Tramadol Hydrochloride RS and USP Tramadol Related Compound A RS in Mobile phase
Standard solution:
6 µg/mL of USP Tramadol Hydrochloride RS in Mobile phase
System sensitivity solution:
Transfer 5 mL of the Standard solution into a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Sample solution:
Finely powder NLT 20 Tablets. Transfer a portion of the powder, equivalent to 200 mg of tramadol hydrochloride, into a 50-mL volumetric flask. Add about 35 mL of Mobile phase, sonicate for 5 min, and shake for 10 min. Dilute with Mobile phase to volume, and mix. Pass a portion of this solution through a suitable filter, and use the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 273 nm
Column:
3.9-mm × 15-cm; packing L7
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution, Standard solution, and System sensitivity solution
Suitability requirements
Resolution:
NLT 2.0 between tramadol related compound A and tramadol, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution; NMT 10%, System sensitivity solution
Analysis
[Note—Disregard any peak that is shown to be due to solvents or excipients. ]
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 0.1
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of tramadol from the Standard solution |
| CS | = | = concentration of USP Tramadol Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of tramadol hydrochloride in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual unspecified impurities:
See Impurity Table 1.
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| RS,SR-1-(3-Methoxyphenyl)-2-(dimethylaminomethyl)cyclohexanol hydrochloridea | 0.85 | 1.0 | 0.2 |
| Tramadol hydrochloride | 1.00 | — | — |
| 1-(3-Methoxyphenyl)-2-(dimethylaminomethyl) cyclohex-1-ene hydrochloride | 5.27 | 1.0 | 0.2 |
| 1-(3-Methoxyphenyl)-2-(dimethylaminomethyl) cyclohex-6-ene hydrochloride | 4.27 | 1.27 | 0.2 |
| Individual unspecified impurity | — | 1.0 | 0.2 |
| Total impurities | — | — | 0.7% |
|
a
Tramadol related compound A.
|
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ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers, and store at controlled room temperature.
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison 1-301-816-8139 |
(SM22010) Monographs - Small Molecules 2 |
| 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 4905
Pharmacopeial Forum: Volume No. 36(6) Page 1577