- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Sertraline Tablets |
Selective serotonin reuptake inhibitor; antidepressant.
Sertraline Tablets contain Sertraline Hydrochloride.
The tablets comply with the requirements stated under Tablets and with the following requirements.
95.0 to 105.0% of the stated amount.
Shake a quantity of the powdered tablets containing 0.25 g of Sertraline Hydrochloride with 10 mL of absolute ethanol for 10 minutes, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of sertraline hydrochloride (RS 443).
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
(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.
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) A suitable solution of sertraline hydrochloride BPCRS in dissolution medium.
(a) 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.
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 chromatogram is recorded under the prescribed conditions the retention time of sertraline is about 2 minutes
Calculate the content of C17H17Cl2N,HCl in the medium using the declared content of C17H17Cl2N,HCl in sertraline hydrochloride BPCRS.
The amount of sertraline hydrochloride released after 30 minutes is not less than 75% (Q) of the stated amount.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in a mixture of 30 volumes of acetonitrile and 70 volumes of water (solvent A).
(1) Shake a quantity of whole tablets containing 500 mg of Sertraline Hydrochloride with 150 mL of solvent 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), discard the first 5 mL of filtrate.
(2) Dilute 1 volume of solution (1) to 500 volumes.
(3) 0.001% w/v solution of (R)-mandelic acid.
(4) Dissolve the contents of a vial of sertraline hydrochloride impurity standard BPCRS in 0.2 mL of solvent A.
(5) Dilute 1 volume of solution (2) to 2 volumes with solvent A.
(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 phases 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 A A 0.272% w/v solution of potassium dihydrogen orthophosphate, adjusted to pH 3.0 with orthophosphoric acid.
Mobile phase B acetonitrile R1
The test is not valid unless the chromatogram obtained with solution (4) closely resembles the reference chromatogram supplied with sertraline hydrochloride impurity standard BPCRS.
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 any 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 peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks excluding the area of any peak corresponding to impurity C is not greater than 7.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%).
Disregard any peak with an area less than that of the principal peak in the chromatogram obtained with solution (5) (0.1%).
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of whole tablets containing 400 mg of Sertraline Hydrochloride with 140 mL of a mixture of 1 volume of acetonitrile and 2 volumes of water until fully dispersed. Mix for 5 minutes with the aid of ultrasound and add sufficient of a mixture of 1 volumes of acetonitrile and 2 volumes of water to produce 200 mL, mix and filter (Whatman PVDF is suitable), discard the first 5 mL of filtrate.
(2) 0.003% w/v of sertraline hydrochloride cis-isomer BPCRS in methanol (10%).
(3) 0.0002% w/v of sertraline hydrochloride BPCRS and 0.0002% w/v of sertraline hydrochloride cis-isomer BPCRS in methanol (10%).
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with silica gel OD for chiral separation (ChromTech Chiral-AGP is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 0.7 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 210 nm.
(f) Inject 40 µL of each solution.
(g) Allow the chromatography to proceed for 30 minutes.
1 volume of propan-2-ol and 9 volumes of a 0.23% w/v solution of ammonium dihydrogen orthophosphate.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 2.5.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to sertraline cis-isomer is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.5%).
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 0.2 g of Sertraline Hydrochloride 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). Discard the first 5 mL of filtrate and dilute 5 volumes of the filtrate to 100 volumes with mobile phase.
(2) 0.005% w/v of sertraline hydrochloride BPCRS in the mobile phase.
The chromatographic conditions described under Dissolution may be used.
Calculate the content of C17H17Cl2N,HCl in the tablets using the declared content of C17H17Cl2N,HCl in sertraline hydrochloride BPCRS.
The impurities limited by the requirements of this monograph include impurities B, C, E and G listed under Sertraline Hydrochloride.
1. (1RS,4RS)-N-methyl-4-phenyl-1,2,3,4-tetrahydronaphthalen-1-amine (Ph. Eur. Impurity B);
2. (1RS,4RS)-4-(4-chlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine (Ph. Eur. Impurity C);
3. (2R)-hydroxyphenylacetic acid ((R)-mandelic acid), (Ph. Eur. Impurity E);
4. (1R,4R)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine (sertraline enantiomer/cis isomer) (Ph. Eur. Impurity G).