Action and use
Benzodiazepine.
Definition
Lorazepam Tablets contain Lorazepam.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of lorazepam, C15H10Cl2N2O2
90.0 to 110.0% of the stated amount.
Identification
A. The
light absorption,
Appendix II B, in the range 210 to 350 nm of the solution obtained in the Assay exhibits two maxima, at 230 nm and 316 nm.
(1) Shake a quantity of the powdered tablets containing 10 mg of Lorazepam with 10 mL of
acetone for 20 minutes, filter and evaporate the filtrate to dryness. Dissolve the residue in 10 mL of
absolute ethanol, add 5 mL of
hydrochloric acid, heat on a water bath for 20 minutes and cool. Transfer the cooled solution to a separating funnel, add 8 mL of 10
m sodium hydroxide, extract with two 25-mL quantities of
ether and filter the combined extracts through absorbent cotton. Evaporate the filtrate to about 2 mL and dilute to 10 mL with
methanol.
(2) Treat 10 mL of a 0.1% w/v solution of
lorazepam BPCRS in
absolute ethanol, add 5 mL of
hydrochloric acid, heat on a water bath for 20 minutes and cool. Transfer the cooled solution to a separating funnel, add 8 mL of 10
m sodium hydroxide, extract with two 25-mL quantities of
ether and filter the combined extracts through absorbent cotton. Evaporate the filtrate to about 2 mL and dilute to 10 mL with
methanol.
chromatographic conditions
(a) Use as the coating
silica gel GF254 (Merck silica gel 60 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 in air, spray with a freshly prepared 1.25% w/v solution of
sodium nitrite in 0.5
m hydrochloric acid. Heat the plate at 100° for 5 minutes, allow to cool and spray with a 0.1% w/v solution of N-
(1-naphthyl)ethylenediamine dihydrochloride in
absolute ethanol.
mobile phase
toluene
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
Dissolution
Carry out the procedure protected from light. 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 1, rotating the basket at 100 revolutions per minute.
procedure
(1) After 45 minutes withdraw a 10 mL sample of the medium. Using 2 cm cells measure the
absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, to produce a solution expected to contain about 0.00011% w/v of Lorazepam, at the maximum at 232 nm,
Appendix II B using 0.1
m hydrochloric acid in the reference cell.
determination of content
Calculate the content of Lorazepam, C15H10Cl2N2O2, in the medium taking 1115 as the value of A(1%, 1cm) at the maximum at 232 nm.
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in acetone.
(1) Shake a quantity of powdered tablets containing 10 mg of Lorazepam with 4 mL of
acetone, centrifuge and use the supernatant liquid.
(3) Dilute 1 volume of solution (1) to 100 volumes.
(4) Dilute 1 volume of solution (1) to 200 volumes.
chromatographic conditions
(b) Use the mobile phase as described below.
(c) Before use, stand the plate in
methanol, allowing the solvent front to ascend 17 cm, heat the plate at 100° to 105° for 1 hour. Use with the flow of mobile phase in the same direction as that used for the prewash.
(d) Apply 40 µL of each solution.
(e) Develop the plate to 17 cm.
mobile phase
10 volumes of methanol and 100 volumes of chloroform.
limits
In the chromatogram obtained with solution (1):
any spot corresponding to 6-chloro-4-(2-chlorophenyl)quinazoline-2-carboxaldehyde is not more intense than the spot in the chromatogram obtained with solution (2) (1%);
any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (3) (1%);
not more than one such spot is more intense than the spot in the chromatogram obtained with solution (4) (0.5%).
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of Lorazepam comply with the requirements stated under Tablets using the following method of analysis. Crush one tablet to a fine powder, add 40 mL of ethanol (96%) and shake for 1 hour. Add sufficient ethanol (96%) to produce 50 mL, centrifuge and dilute the supernatant liquid with sufficient ethanol (96%) to produce a solution containing 0.0005% w/v of Lorazepam. Measure the absorbance of the resulting solution at the maximum at 230 nm, Appendix II B, and calculate the content of C15H10Cl2N2O2 taking 1150 as the value of A(1%, 1 cm) at the maximum at 230 nm.
Assay
Weigh and powder 20 tablets. To a quantity of the powdered tablets containing 5 mg of Lorazepam add 40 mL of ethanol (96%) and shake for 1 hour. Add sufficient ethanol (96%) to produce 50 mL, centrifuge, dilute 5 mL to 100 mL with the same solvent and measure the absorbance of the resulting solution at the maximum at 230 nm, Appendix II B. Calculate the content of C15H10Cl2N2O2 taking 1150 as the value of A(1%, 1 cm) at the maximum at 230 nm.
Storage
Lorazepam Tablets should be protected from light.