Action and use
Benzodiazepine.
Definition
Loprazolam Tablets contain Loprazolam Mesilate.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of loprazolam, C23H21ClN6O3
90.0 to 110.0% of the stated amount.
Identification
A. The
light absorption, Appendix II B, in the range 210 to 370 nm of the filtrate obtained in the Assay exhibits a maximum at 330 nm and a shoulder at 240 nm.
(1) Shake a quantity of the powdered tablets containing the equivalent of 2 mg of loprazolam with 10 mL of a mixture of 46 volumes of
chloroform, 46 volumes of
methanol and 8 volumes of
water, centrifuge and use the clear supernatant liquid.
(2) 0.02% w/v of loprazolam mesilate BPCRS in the same solvent mixture.
chromatographic conditions
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
mobile phase
20 volumes of methanol and 80 volumes of chloroform.
confirmation
The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).
Tests
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in a mixture of 46 volumes of chloroform, 46 volumes of methanol and 8 volumes of water.
(1) Shake a quantity of the powdered tablets containing the equivalent of 10 mg of loprazolam with 4 mL of the solvent mixture, mix the suspension with the aid of ultrasound for 5 minutes, centrifuge and use the clear supernatant liquid.
(2) 0.00025% w/v of loprazolam mesilate BPCRS.
chromatographic conditions
(a) Use as the coating
silica gel (Merck silica gel 60 plates are suitable). Before use, stand the plate in
methanol, allowing the solvent front to ascend 17 cm, allow to dry in air, heat the plate at 100° to 105° for 1 hour and use with the flow of mobile phase in the same direction as that used for the pretreatment.
(b) Use the mobile phase as described below.
(c) Apply 40 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air, spray the plate with a 5% w/v solution of
titanium(III) chloride in a solution of hydrochloric acid containing 10% w/v of HCl and then spray with a solution containing 0.4 g of
4-dimethyl-aminocinnamaldehyde in a mixture of 20 mL of 6
Mhydrochloric acid and 100 mL of
ethanol (96%). Heat at 100° until spots appear (about 10 minutes).
mobile phase
20 volumes of methanol and 80 volumes of chloroform.
limits
In the chromatogram obtained with solution (1):
any spot corresponding to the dimethylamino analogue is not more intense than the spot in the chromatogram obtained with solution (3) (0.5%);
any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (2) (0.1%).
Uniformity of content
Tablets containing less than the equivalent of 2 mg and/or less than 2% w/w of loprazolam comply with the requirements stated under Tablets using the following method of analysis. Shake one tablet with 8 mL of water, add 80 mL of absolute ethanol, mix with the aid of ultrasound for 10 minutes, cool and dilute to 200 mL with absolute ethanol. Mix, filter, discarding the first 20 mL of filtrate, and measure the absorbance of the resulting solution at the maximum at 330 nm, Appendix II B. Calculate the content of C23H21ClN6O3 taking 890 as the value of A(1%, 1 cm) at the maximum at 330 nm.
Assay
Use the average of the individual results determined in the test for Uniformity of content.
Labelling
The quantity of active ingredient is stated in terms of the equivalent amount of loprazolam.