Action and use
Benzodiazepine.
Definition
Lormetazepam Tablets contain Lormetazepam.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of lormetazepam, C16H12Cl2N2O2
95.0 to 105.0% of the stated amount.
Identification
A. Shake a quantity of the powdered tablets containing 10 mg of Lormetazepam with 5 mL of
acetone, filter, wash the residue with a further 5 mL of
acetone, combine the acetone extracts and evaporate to dryness on a water bath using a current of
nitrogen. The
infrared absorption spectrum of the dried residue,
Appendix II A, is concordant with the
reference spectrum of lormetazepam
(RS 207).
(1) Shake a quantity of the powdered tablets containing 10 mg of Lormetazepam with 5 mL of
acetone for 15 minutes and filter.
(2) 0.2% w/v of
lormetazepam BPCRS in
acetone.
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
1 volume of methanol and 10 volumes of chloroform.
confirmation
The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).
Tests
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dissolve a quantity of the powdered tablets containing 10 mg of Lormetazepam in 100 mL of
methanol (60%), centrifuge and use the clear supernatant liquid.
(2) Dilute 1 volume of solution (1) to 100 volumes with
methanol (60%).
chromatographic conditions
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 230 nm.
(f) Inject 20 µL of each solution.
mobile phase
48 volumes of methanol and 52 volumes of a phosphate buffer prepared by dissolving 4.91 g of sodium dihydrogen orthophosphate and 0.633 g of disodium hydrogen orthophosphate in sufficient water to produce 1000 mL.
system suitability
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 4.
limits
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than 0.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the sum of the areas of any secondary peaks is not greater than the area of the peak in the chromatogram obtained with solution (2) (1%).
Disregard any peaks with a retention time of less than half that of lormetazepam.
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of Lormetazepam comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add 3 mL of
water to one tablet, allow to stand for 20 minutes with occasional shaking, mix with the aid of ultrasound for 2 minutes, add 35 mL of
methanol, mix with the aid of ultrasound for 5 minutes, shake for a further 15 minutes and cool. For tablets containing 0.5 mg of Lormetazepam, dilute the resulting solution to 50 mL with
water and for tablets containing 1 mg of Lormetazepam, dilute to 100 mL with
methanol (60%), centrifuge for 10 minutes and use the clear supernatant liquid.
(2) 0.001% w/v of
lormetazepam BPCRS in
methanol (70%).
chromatographic conditions
The chromatographic conditions described under Related substances may be used.
determination of content
Calculate the content of C16H12Cl2N2O2 in the tablets from the declared content of C16H12Cl2N2O2 in lormetazepam BPCRS.
Assay
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Disperse a quantity of the powdered tablets containing 10 mg of Lormetazepam in 500 mL of
methanol (60%), centrifuge for 15 minutes and use the clear supernatant liquid.
(2) 0.002% w/v of
lormetazepam BPCRS in
methanol (60%).
chromatographic conditions
The chromatographic conditions described under Related substances may be used.
determination of content
Calculate the content of C16H12Cl2N2O2 in the tablets from the declared content of C16H12Cl2N2O2 in lormetazepam BPCRS.