(tram' a dol hye'' droe klor' ide).
(±)-cis-2-[(Dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol hydrochloride;
(±)-cis-2-[(Dimethylamino)methyl]-1-(m-methoxyphenyl) cyclohexanol hydrochloride [36282-47-0].
Tramadol Hydrochloride contains NLT 98.0% and NMT 102.0% of C16H25NO2·HCl, calculated on the anhydrous basis.
• B. Identification TestsGeneral, Chloride 191: An aqueous solution (1 in 100) meets the requirements.
Solution A: Dissolve 0.5 mL of trifluoroacetic acid in 1000 mL of water.
Mobile phase: Acetonitrile and Solution A (30:70)
System suitability solution: 0.05 mg/mL each of USP Tramadol Hydrochloride RS and USP Tramadol Hydrochloride Related Compound A RS in Mobile phase
Standard solution: 1.5 mg/mL USP Tramadol Hydrochloride RS in Mobile phase
Sample solution: 1.5 mg/mL tramadol hydrochloride in Mobile phase
Detector: UV 270 nm
Column: 4.6-mm × 25-cm; 5-µm packing L1
Flow rate: 1 mL/min
Injection size: 20 µL
Sample: System suitability solution
[NoteThe relative retention times for tramadol related compound A and tramadol are about 0.9 and 1.0, respectively. ]
Resolution: NLT 2.0 between tramadol related compound A and tramadol
Relative standard deviation: NMT 2.0%
Samples: Standard solution and Sample solution
Calculate the percentage of C16H25NO2·HCl in the portion of Tramadol Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria: 98.0%102.0% on the anhydrous basis
• Residue on Ignition 281: NMT 0.1%
• Heavy Metals, Method I 231: 20 ppm
• Content of Chloride
Sample solution: 150 mg of Tramadol Hydrochloride in 40 mL of water
Analysis: To the Sample solution add, with stirring, 7.5 mL of 4 N nitric acid and 15.0 mL of 0.1 N silver nitrate, and titrate with 0.1 N ammonium thiocynate VS, determining the endpoint potentiometrically, and using a silverglass electrode system. Each mL of 0.1 N ammonium thiocynate is equivalent to 3.545 mg of chloride.
Acceptance criteria: 11.6%12.1% of chloride is found.
• Procedure 1: Limit of Tramadol Related Compound B (2-(dimethylaminomethyl)-1-cyclohexanone hydrochloride)
Adsorbent: 0.25-mm layer of chromatographic silica gel mixture
Standard solution: 0.1 mg/mL USP Tramadol Related Compound B RS in methanol
Sample solution: 50 mg/mL Tramadol Hydrochloride in methanol
Developing solvent system: Toluene, isopropyl alcohol, and 25% ammonia water (80:19:1)
Sodium nitrite solution: 50 mg/mL sodium nitrite in water
Analysis: Separately apply about 10 µL each of the Sample solution and the Standard solution to the plate, and develop the plate until the solvent front is 10 cm above the line of application. Remove the plate, spray with Dragendorff's TS, and air-dry for 5 min. Spray the dried plate with Sodium nitrite solution until the spot from tramadol related compound B in the Standard solution is visible. Any secondary spot from the Sample solution corresponding to tramadol related compound B is not more intense than a corresponding spot from the Standard solution.
Acceptance criteria: NMT 0.2%
• Procedure 2
Mobile phase, System suitability solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.
Sample: Sample solution
Calculate the percentage of each impurity in the portion of Tramadol Hydrochloride taken:
Result = (rU/rT) × 100
Tramadol related compound A: NMT 0.2%
Individual impurities: NMT 0.1%
Total impurities: NMT 0.4%
• Water Determination, Method Ia 921: NMT 0.5%
Sample solution: 500 mg of Tramadol Hydrochloride in 10 mL of water
Analysis: To the Sample solution add 0.2 mL of methyl red TS and 0.2 mL of 0.01 N hydrochloric acid VS, and titrate with 0.01 N sodium hydroxide VS.
Acceptance criteria: NMT 0.4 mL of 0.01 N sodium hydroxide is required to produce a yellow color.
• Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.
• USP Reference Standards 11
USP Tramadol Related Compound A RS
USP Tramadol Related Compound B RS
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 4904Pharmacopeial Forum: Volume No. 34(5) Page 1200