Fluvoxamine Tablets

General Notices

Action and use

Selective serotonin reuptake inhibitor; antidepressant.

Definition

Fluvoxamine Tablets contain Fluvoxamine Maleate.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of fluvoxamine maleate, C15H21F3N2O2,C4H4O4

92.5 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 50 mg of Fluvoxamine Maleate with 10 mL of acetonitrile for 10 minutes, centrifuge and evaporate the supernatant liquid to dryness using a rotary evaporator. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of fluvoxamine maleate (RS 159).
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of water, at a temperature of 37°, as the medium.
procedure

After 20 minutes withdraw a 10-mL sample of the medium and centrifuge. Measure the absorbance of the clear supernatant liquid, suitably diluted with water if necessary, at the maximum at 244 nm, Appendix II B using water in the reference cell.

determination of content

Calculate the total content of fluvoxamine maleate, C15H21F3N2O2,C4H4O4, in the medium taking 270 as the value of A(1%, 1 cm) at the maximum at 244 nm.

Related substances

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

(1) Shake a quantity of the powdered tablets containing 0.25 g of Fluvoxamine Maleate with 125 mL of the mobile phase for 10 minutes, add sufficient mobile phase to produce 250 mL, mix, centrifuge and use the supernatant liquid.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.
(3) Heat a 0.32% w/v solution of fluvoxamine maleate impurity standard BPCRS in 0.1m hydrochloric acid on a water bath for 10 minutes (generation of impurity C).
(4) 0.0008% w/v of fluvoxamine impurity D BPCRS in the mobile phase.
(5) Dilute 1 volume of solution (2) to 10 volumes with the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (15 cm × 3 mm) packed with end-capped octylsilyl silica gel for chromatography (5 µm) (Zorbax C8 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 a column temperature of 35°.
(e) Use a detection wavelength of 254 nm.
(f) Inject 5 µL of each solution.
(g) Allow the chromatography to proceed for 2.5 times the retention time of fluvoxamine.
mobile phase

40 volumes of a solution containing 1.25% w/v of diammonium hydrogen orthophosphate and 0.275% w/v of sodium heptanesulfonate monohydrate and 60 volumes of methanol, adjusting the pH of the mixture to 3.5 with orthophosphoric acid.

When the chromatograms are recorded under the prescribed conditions, the relative retention times with reference to fluvoxamine (retention time about 8 minutes) are: maleic acid, about 0.2; impurity C, about 0.6; impurity F, about 0.7; impurity B, about 0.8; impurity D, about 1.6 and impurity A, about 2.0.

system suitability

The test is not valid unless, the chromatogram obtained with solution (3):

closely resembles the reference chromatogram supplied with fluvoxamine maleate impurity standard BPCRS;

the resolution between the peaks corresponding to fluvoxamine and impurity B is at least 1.5.

limits

Identify the impurities from the chromatogram obtained with solution (3) and from the reference chromatogram supplied with the reference material.

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurity C is not greater than 3 times the area of the principal peak in the chromatogram obtained with solution (2) (3%);

the area of any peak corresponding to impurity B is not greater than half the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);

the area of any peak corresponding to impurity D is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (0.8%);

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

the sum of the areas of all the secondary peaks, other than any peaks corresponding to impurity C and impurity D, is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).

Disregard the peak corresponding to maleic acid and any peak with an area less than the area 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) Shake a quantity of the powdered tablets containing 0.25 g of Fluvoxamine Maleate with 125 mL of the mobile phase for 10 minutes, add sufficient of the mobile phase to produce 250 mL, mix, centrifuge and dilute 1 volume of the supernatant liquid to 10 volumes with the mobile phase.
(2) 0.010% w/v of fluvoxamine maleate BPCRS in the mobile phase.
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

determination of content

Calculate the content of C15H21F3N2O2,C4H4O4 in the tablets using the declared content of C15H21F3N2O2,C4H4O4 in fluvoxamine maleate BPCRS.

Storage

Fluvoxamine Tablets should be protected from light.

IMPURITIES

The impurities limited by the requirements of this monograph include impurities A, B, C, D, E and F listed under Fluvoxamine Maleate.