Action and use
Selective serotonin reuptake inhibitor; antidepressant.
DEFINITION
Sertraline Tablets contain Sertraline Hydrochloride.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of sertraline, C17H17Cl2N
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing the equivalent of 0.22 g of sertraline with 10 mL of absolute ethanol for 10 minutes and filter. Evaporate the filtrate to dryness and dry the residue at 60° under vacuum for 1 hour. The infrared absorption spectrum of the residue, Appendix II A, is concordant with reference spectrum A of sertraline hydrochloride (RS 460). If the spectrum thus obtained is not concordant, record a solution spectrum using a 1.0% w/v solution of the residue obtained above in dichloromethane. The infrared absorption spectrum of the resulting solution, Appendix II A, is concordant with reference spectrum B of sertraline hydrochloride (RS 443).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 75 revolutions per minute.
(b) Use 900 mL of sodium acetate buffer solution pH 4.5, at a temperature of 37°, as the medium.
PROCEDURE
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 30 minutes withdraw a 10-mL sample of the medium and filter (Whatman GF/C is suitable), discard the first 5 mL of filtrate.
(2) 0.0056% w/v of sertraline hydrochloride BPCRS in dissolution medium.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (4 μm) (Novapak C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.8 mL per minute.
(d) Use a column temperature 30°.
(e) Use a detection wavelength of 265 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
15 volumes of methanol, 40 volumes of a solution containing 0.286% v/v glacial acetic acid and 0.348% v/v triethylamine and 45 volumes of acetonitrile.
When the chromatograms are recorded under the prescribed conditions the retention time of sertraline is about 2 minutes.
DETERMINATION OF CONTENT
Calculate the content of sertraline, C17H17Cl2N, in the medium using the declared content of C17H17Cl2N,HCl in sertraline hydrochloride BPCRS. Each mg of C17H17Cl2N,HCl is equivalent to 0.8936 mg of C17H17Cl2N.
LIMITS
The amount of sertraline released after 30 minutes is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Solution A 30 volumes of acetonitrile and 70 volumes of water.
(1) Shake a quantity of whole tablets containing the equivalent of 0.45 g of sertraline with 150 mL of solution A until fully dispersed. Mix for 5 minutes with the aid of ultrasound and add sufficient solvent A to produce 200 mL, mix and filter (Whatman PVDF is suitable), discarding the first 5 mL of filtrate.
(2) Dilute 1 volume of solution (1) to 500 volumes with solution A.
(3) 0.001% w/v of (R)-mandelic acid in solution A.
(4) 0.25% w/v of sertraline hydrochloride impurity standard BPCRS in solution A.
(5) Dilute 1 volume of solution (2) to 2 volumes with solution A.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Symmetry C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 210 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
Mobile phase A: 0.272% w/v of potassium dihydrogen orthophosphate in water, adjusted to pH 3.0 with orthophosphoric acid.
Mobile phase B: acetonitrile R1
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-30 | 70 | 30 | isocratic |
| 30-40 | 70→60 | 30→40 | linear gradient |
| 40-41 | 60→70 | 40→30 | linear gradient |
| 41-50 | 70 | 30 | re-equilibration |
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (4) closely resembles the reference chromatogram supplied with sertraline hydrochloride impurity standard BPCRS.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity C is not greater than 4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.8%);
the area of any peak corresponding to (R)-mandelic acid is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.4%);
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 total impurity content, excluding impurity C, is not greater than 1.5%.
Disregard any peak with an area less than that of the principal peak in the chromatogram obtained with solution (5) (0.1%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Mix for 45 minutes with the aid of ultrasound a quantity of the powdered tablets containing the equivalent of 0.19 g of sertraline with 150 mL of mobile phase, shake for 30 minutes, cool, add sufficient water to produce 200 mL, mix and filter (Whatman GF/C is suitable), discarding the first 5 mL of filtrate. Dilute 1 volume of the filtrate to 20 volumes with mobile phase.
(2) 0.005% w/v of sertraline hydrochloride BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used.
DETERMINATION OF CONTENT
Calculate the content of C17H17Cl2N in the tablets using the declared content of C17H17Cl2N,HCl in sertraline hydrochloride BPCRS. Each mg of C17H17Cl2N,HCl is equivalent to 0.8936 mg of C17H17Cl2N.
LABELLING
The quantity of the active ingredient is stated in terms of the equivalent amount of sertraline.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities B, C and E listed under Sertraline Hydrochloride.
