Tramadol Capsules

General Notices

Action and use

µ-Opioid receptor (OP₃, MOR) agonist and noradrenaline reuptake inhibitor; analgesic.

DEFINITION

Tramadol Capsules contain Tramadol Hydrochloride.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of tramadol hydrochloride, C₁₆H₂₅NO_2,HCl

95.0 to 105.0% of the stated amount.

Identification

Shake a quantity of the capsules containing 50 mg of Tramadol Hydrochloride with 25 mL of methanol for 5 minutes, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of tramadol hydrochloride (RS 465).

TESTS

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Mix with the aid of ultrasound, a quantity of the contents of the capsules containing 0.5 g of Tramadol Hydrochloride with 80 mL of the mobile phase, cool, add sufficient mobile phase to produce 100 mL and filter through a glass-fibre filter (Whatman GF/A is suitable).

(2) Dilute 2 volumes of solution (1) to 100 volumes with the mobile phase and further dilute 1 volume to 10 volumes with the mobile phase.

(3) 0.0015% w/v of tramadol impurity A BPCRS in the mobile phase.

(4) 0.0015% w/v each of tramadol hydrochloride BPCRS and tramadol impurity A BPCRS in the mobile phase.

chromatographic conditions

(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Waters Symmetry C18 is suitable).

(b) Use isocratic elution and the mobile phase described below.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 271 nm.

(f) Inject 20 µL of each solution.

(g) For solution (1) allow the chromatography to proceed for four times the retention time of the principal peak.

mobile phase

1 volume of trifluoroacetic acid, 30 volumes of acetonitrile and 69 volumes of water.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (4), the resolution factor between the two principal peaks is at least 3.0.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to tramadol impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.3%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);

the sum of the areas of any secondary peaks is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (1%).

Disregard any peak with an area less than 0.5 times that of the principal peak in the chromatogram obtained with solution (2) (0.1%)

ASSAY

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Mix with the aid of ultrasound, a quantity of the mixed contents of 20 capsules containing 50 mg of Tramadol Hydrochloride with 150 mL of the mobile phase, cool, add sufficient mobile phase to produce 200 mL and filter through a glass-fibre filter (Whatman GF/A is suitable).

(2) 0.025% w/v of tramadol hydrochloride BPCRS in the mobile phase.

(3) 0.0015% w/v each of tramadol hydrochloride BPCRS and tramadol impurity A BPCRS in the mobile phase.

chromatographic conditions

The chromatographic procedure described under Related substances may be used.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 3.0.

determination of content

Calculate the content of C₁₆H₂₅NO₂,HCl using the declared content of C₁₆H₂₅NO₂,HCl in tramadol hydrochloride BPCRS.

Impurities

The impurities limited by the requirements of this monograph include those listed under Tramadol Hydrochloride.