Levomepromazine Tablets

General Notices

Action and use

Dopamine receptor antagonist; neuroleptic.

Definition

Levomepromazine Tablets contain Levomepromazine Maleate.

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

Content of levomepromazine maleate, C19H24N2OS,C4H4O4

95.0 to 105.0% of the stated amount.

Identification

A. To a quantity of the powdered tablets containing 50 mg of Levomepromazine Maleate add 10 mL of water and 2 mL of 1m sodium hydroxide, shake, extract with 15 mL of ether and allow to separate. Wash the ethereal layer with 5 mL of water, filter through phase-separating paper (Whatman 1 PS is suitable) containing anhydrous sodium sulfate, evaporate the ether to dryness and dry the residue at 100° for 3 hours. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of levomepromazine (RS 404).
B. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Mix a quantity of the powdered tablets containing 0.2 g of Levomepromazine Maleate with 10 mL of a mixture of 1 volume of water and 9 volumes of acetone, shake with the aid of ultrasound for 5 minutes, allow to stand and use the clear supernatant liquid.
(2) 0.6% w/v of maleic acid in anhydrous formic acid.
chromatographic conditions
(a) Use as the coating TLC silica gel F254 (Macherey-Nagel plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry at 120° for 10 minutes and examine under ultraviolet light (254 nm).
mobile phase

3 volumes of water, 7 volumes of anhydrous formic acid and 90 volumes of di-isopropyl ether.

confirmation

The chromatogram obtained with solution (1) shows a spot remaining on the line of application and a spot which is similar in position to the principal spot 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 500 mL of 0.1m hydrochloric acid, at a temperature of 37°, as the medium.
procedure
(1) After 30 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 311 nm, Appendix II B using 0.1m hydrochloric acid in the reference cell.
(2) Measure the absorbance of a suitable solution of levomepromazine maleate BPCRS at the maximum at 311 nm, Appendix II B, using 0.1m hydrochloric acid in the reference cell.
determination of content

Calculate the total content of levomepromazine maleate, C19H24N2OS,C4H4O4, in the medium from the absorbances obtained and using the declared content of C19H24N2OS,C4H4O4 in levomepromazine maleate BPCRS. The amount of levomepromazine maleate released is not less than 60% of the stated amount.

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, protected from light using the following solutions.

(1) Mix a quantity of the powdered tablets containing 0.1 g of Levomepromazine Maleate with 10 mL of a mixture of 1 volume of 18m ammonia and 99 volumes of methanol, shake with the aid of ultrasound for 5 minutes, mix, filter (Whatman No. 40 paper is suitable), discarding the first portion of filtrate, and use the filtrate.
(2) Dilute 1 volume of solution (1) to 200 volumes with the same solvent.
chromatographic conditions
(a) Use as the coating TLC silica gel GF254.
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air and examine under ultraviolet light (254 nm).
mobile phase

5 volumes of diethylamine, 10 volumes of acetone and 85 volumes of toluene.

limits

Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%).

Assay

Carry out the following procedure protected from light. Weigh and powder 20 tablets. To a quantity of the powdered tablets containing 50 mg of Levomepromazine Maleate add 15 mL of 0.2m methanolic ammonia, stir for 2 minutes, filter and collect the filtrate. Repeat the extraction with a further 3 successive 15-mL quantities of 0.2m methanolic ammonia, grinding the residue with a glass rod before extraction. Dilute the combined filtrates to 100 mL with 0.2m methanolic ammonia, mix and dilute 10 volumes of the solution to 100 volumes with methanol and further dilute 10 volumes of this solution to 100 volumes with the same solvent. Measure the absorbance of this solution at the maximum at 254 nm, Appendix II B, using methanol in the reference cell. Measure the absorbance of a 0.0005% w/v solution of levomepromazine maleate BPCRS in 0.002m methanolic ammonia at the same wavelength using methanol in the reference cell and calculate the content of C19H24N2OS,C4H4O4 in the tablets using the declared content of C19H24N2OS,C4H4O4 in levomepromazine maleate BPCRS.

Storage

Levomepromazine Tablets should be protected from light.