Action and use
Monoamine oxidase type B inhibitor; treatment of Parkinson’s disease.\
DEFINITION
Selegiline Oral Solution is a solution of Selegiline Hydrochloride in a suitable flavoured vehicle.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.
Content of selegiline hydrochloride, C13H18ClN
90.0 to 105.0% of the stated amount.
IDENTIFICATION
A. In the Assay, the principal peak in the chromatogram obtained with solution (1) has the same retention time as the principal peak in the chromatogram obtained with solution (2).
B. In the test for Related substances, the principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).
TESTS
(S)-Selegiline
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add to a weighed quantity of the oral solution containing 20 mg of Selegiline Hydrochloride 1 mL of propan-2-ol and 10 μL of butylamine, dilute to 20 mL with the mobile phase, shake thoroughly, filter and use the filtrate.
(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 20 mL with the mobile phase.
(3) Dilute 0.5 mL of solution (2) to 20 mL with the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with silica gel OD for chiral separation (Chiralcel OD is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 0.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
0.2 volume of propan-2-ol and 99.8 volumes of cyclohexane
SYSTEM SUITABILITY
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, in the chromatogram obtained with solution (2), the resolution factor between the peaks corresponding to (S)-selegiline and (R)-selegiline is at least 1.5. If necessary, adjust the concentration of propan-2-ol in the mobile phase.
LIMITS
In the chromatogram obtained with solution (1):
The area of 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 thin-layer chromatography, Appendix III A, using the following solutions.
(1) Adjust the pH of a quantity of the oral solution containing 10 mg of Selegiline Hydrochloride to 12 with 1M sodium hydroxide, add 2 mL of chloroform, shake for 30 minutes, allow to separate and use the chloroform layer.
(2) Prepare solution (2) in the same manner as solution (1) but using 4 mL of a 0.25% w/v solution of selegiline hydrochloride BPCRS in 0.1M hydrochloric acid in place of the oral solution.
(3) Adjust the pH of 1 mL of a 0.025% w/v solution of selegiline hydrochloride BPCRS in 0.1M hydrochloric acid to 12 with 1M sodium hydroxide, add 10 mL of chloroform, shake for 30 minutes, allow to separate and use the chloroform layer.
(4) Dilute 2 volumes of solution (3) to 5 volumes with chloroform.
(5) Adjust the pH of 2 mL of a 0.025% w/v solution of methylamphetamine hydrochloride in 0.1M hydrochloric acid to 12 with 1M sodium hydroxide, add 10 mL of chloroform, shake for 30 minutes, allow to separate and use the chloroform layer.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating TLC silica gel F254 plate.
(b) Use the mobile phase as described below.
(c) Apply 50 μL of each solution.
(d) Develop the plate to 155 cm.
(e) After removal of the plate, dry in air, spray with a solution prepared by mixing 2 volumes of a solution in acetone containing 10% w/v of iron(III) chloride and 4% w/v of iodine and 1 volume of a 40% w/v solution of (+)-tartaric acid in water and allowing to stand for 15 minutes before use. Examine the plate in daylight immediately after spraying.
MOBILE PHASE
0.5 volume of 13.5M ammonia, 10 volumes of 1,4-dioxan, 10 volumes of propan-2-ol, 10 volumes of toluene and 30 volumes of xylene. Use an unlined tank and add the mobile phase immediately before placing the plate in the tank.
LIMITS
In the chromatogram obtained with solution (1): any spot corresponding to methylamphetamine is not more intense than the spot in the chromatogram obtained with solution (5) (1%); any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (3) (0.5%) and not more than two such spots are more intense than the spot in the chromatogram obtained with solution (4) (0.2%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add 10 mL of a mixture of equal volumes of acetonitrile and methanol to a weighed quantity of the oral solution containing 10 mg of Selegiline Hydrochloride, mix with the aid of ultrasound for 5 minutes, add 40 mL of a mixture of equal volumes of acetonitrile and methanol and shake mechanically for 15 minutes. Add sufficient water to produce 100 mL and
dilute 5 volumes of the resulting solution to 10 volumes with the mobile phase.
(2) 0.005% w/v of selegiline hydrochloride BPCRS in the mobile phase.
(3) 0.005% w/v of selegiline hydrochloride BPCRS and 0.001% w/v of nortriptyline hydrochloride BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 μm).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 215 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
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.
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
Determine the weight per mL of the oral solution, Appendix V G, and calculate the content of C13H18ClN, weight in volume, using the declared content of C13H18ClN in selegiline hydrochloride BPCRS.
STORAGE
Selegiline Oral Solution should not be refrigerated.
