Selegiline Tablets
Action and use
Monoamine oxidase type B inhibitor; treatment of Parkinson’s disease.
Definition
Selegiline Tablets contain Selegiline Hydrochloride.
Content of selegiline hydrochloride, C13H18ClN
95.0 to 105.0% of the stated amount.
Identification
Tests
(S)-Selegiline
Carry out the method for liquid chromatography, Appendix III A, using the following solutions. For solution (1) add to a quantity of the powdered tablets containing 20 mg of Selegiline Hydrochloride 1 mL of propan-2-ol and 10 µL of butylamine, dilute to 10 mL with the mobile phase, shake thoroughly, filter and use the filtrate. For solution (2) dissolve 8 mg of (RS)-selegiline hydrochloride EPCRS in a mixture of 10 µL of butylamine and 1 mL of propan-2-ol and dilute to 10 mL with the mobile phase. For solution (3) dilute 0.5 mL of solution (2) to 20 mL with the mobile phase.
The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with silica gel OD for chiral separation (Chiralcel OD is suitable), (b) as the mobile phase with a flow rate of 0.5 mL per minute a mixture of 0.2 volumes of propan-2-ol and 99.8 volumes of cyclohexane and (c) a detection wavelength of 220 nm.
Inject 20 µL of each solution. When the chromatograms are recorded in the prescribed conditions, the retention time of (S)-selegiline is about 10 minutes. Adjust the sensitivity of the system so that the height of the peaks in the chromatogram obtained with solution (3) is about 10% of the full scale of the recorder. The test is not valid unless the resolution factor between the peaks corresponding to (S)-selegiline and (R)-selegiline in the chromatogram obtained with solution (2) is at least 1.5. If necessary, adjust the concentration of propan-2-ol in the mobile phase.
In the chromatogram obtained with solution (1), any peak corresponding to (S)-selegiline is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.5%).
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered tablets containing 20 mg of Selegiline Hydrochloride with 10 mL of a mixture of equal volumes of methanol and acetonitrile, filter and dilute 5 mL of the filtrate to 10 mL with water. For solution (2) dilute 1 volume of solution (1) to 10 volumes with the mobile phase and dilute 1 volume of this solution to 50 volumes with the mobile phase. Solution (3) contains 0.001% w/v of methylamphetamine hydrochloride in the mobile phase. Solution (4) contains 0.005% w/v of selegiline hydrochloride BPCRS and 0.001% w/v of nortriptyline hydrochloride BPCRS in the mobile phase.
The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm), (b) as the mobile phase with a flow rate of 1 mL per minute a mixture prepared in the following manner: dilute 250 mL of methanol and 250 mL of acetonitrile to 1000 mL with a solution prepared by dissolving 4 mL of butylamine in 900 mL of water, adjusting the pH to 6.5 with acetic acid, and adding sufficient water to produce 1000 mL and (c) a detection wavelength of 215 nm.
Inject 20 µL of each solution. 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.
For solution (1) allow the chromatography to proceed for at least 2.5 times the retention time of the principal peak. In the chromatogram obtained with solution (1) the area of any secondary peak is not greater than 2.5 times the area of the peak in the chromatogram obtained with solution (2) (0.5%), the area of not more than two such peaks is greater than half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%) and the sum of the areas of any such peaks is not greater than six times the area of the principal peak in the chromatogram obtained with solution (2) (1.2%).
If, in the chromatogram obtained with solution (1), the area of any peak corresponding to methylamphetamine is greater than half the area of the peak in the chromatogram obtained with solution (3), the following limits apply. The area of any peak corresponding to methylamphetamine is not greater than the area of the peak in the chromatogram obtained with solution (3) (1%), the area of any other secondary peak is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%) and the sum of the areas of any such peaks is not greater than five times the area of the principal peak in the chromatogram obtained with solution (2) (1%). In each case, disregard any peak with an area less than 0.1 times that of the area of the principal peak in the chromatogram obtained with solution (2) (0.02%).
Assay
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered tablets containing 10 mg of Selegiline Hydrochloride with 100 mL of a mixture of equal volumes of methanol and acetonitrile, filter and dilute 50 mL of the filtrate to 100 mL with water. Solution (2) contains 0.005% w/v of selegiline hydrochloride BPCRS in the mobile phase. Solution (3) contains 0.005% w/v of selegiline hydrochloride BPCRS and 0.001% w/v of nortriptyline hydrochloride BPCRS in the mobile phase.
The chromatographic conditions described under Related substances may be used.
The assay is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 3.0.
Calculate the content of C13H18ClN in the tablets from the chromatograms obtained and using the declared content of C13H18ClN in selegiline hydrochloride BPCRS.
Storage
Selegiline Tablets should be protected from light and moisture.