Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Benzodiazepine.
DEFINITION
Temazepam Oral Solution is a solution of Temazepam in a suitable flavoured vehicle.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.
Content of temazepam, C16H13ClN2O2
90.0 to 110.0% of the stated amount.
IDENTIFICATION
A. Dilute a quantity of the oral solution with sufficient 0.1M methanolic hydrochloric acid to produce a solution containing 0.001% w/v of Temazepam. The light absorption of the resulting solution, Appendix II B, in the range 210 to 400 nm exhibits three maxima, at 238 nm, 283 nm and 358 nm.
B. Carry out the method for thin-layer chromatography, Appendix III A, using a silica gel F254 precoated plate (Merck silica gel 60 F254 plates are suitable) and a mixture of 50 volumes of cyclohexane, 40 volumes of chloroform and 10 volumes of diethylamine as the mobile phase. Apply separately to the plate 2 µL of each of the following solutions. For solution (1) add 5 mL of water to a quantity of the oral solution containing 10 mg of Temazepam and extract with two 10-mL quantities of ether. Evaporate the combined ether extracts almost to dryness and dissolve the residue in 2 mL of acetone. Solution (2) contains 0.5% w/v of temazepam BPCRS in acetone. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm). The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).
C. In the Assay, the chromatogram obtained with solution (2) exhibits a peak with the same retention time as that due to temazepam in the chromatogram obtained with solution (1).
TESTS
Alkalinity
pH, 7.3 to 8.3, Appendix V L.
6-Chloro-1,4-dihydro-1-methyl-4-phenylquinazolin-4-ol
Carry out the method for thin-layer chromatography, Appendix III A, using a silica gel precoated plate (Merck silica gel 60 F254 plates are suitable) and a mixture of 92.5 volumes of chloroform and 7.5 volumes of methanol as the mobile phase but allowing the solvent front to ascend 12 cm above the line of application. Apply separately to the plate 10 µL of each of the following solutions. For solution (1) add 5 mL of water to a quantity of the oral solution containing 10 mg of Temazepam and extract with two 10-mL quantities of ether. Evaporate the combined ether extracts almost to dryness and dissolve the residue in 1 mL of acetone. Solution (2) contains 0.010% w/v of 6-chloro-1,4-dihydro-1-methyl-4-phenylquinazolin-4-ol BPCRS. After removal of the plate, allow it to dry in a current of warm air and examine under ultraviolet light (365 nm). In the chromatogram obtained with solution (1) any spot corresponding to 6-chloro-1,4-dihydro-1-methyl-4-phenylquinazolin- 4-ol is not more intense than the spot in the chromatogram obtained with solution (2).
5-Chloro-2-methylaminobenzophenone
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Solution (1) contains 0.00050% w/v of 5-chloro-2-methylaminobenzophenone BPCRS in methanol (50%). For solution (2) dilute a quantity of the oral solution with sufficient methanol (50%) to produce a solution containing 0.020% w/v of Temazepam.
The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 5 mm) packed with end- capped octadecylsilyl silica gel for chromatography (5 µm) (Lichrosorb RP-18 is suitable), (b) a mixture of 75 volumes of methanol, 25 volumes of water and 0.03 volume of diethylamine as the mobile phase with a flow rate of 1.5 mL per minute and (c) a detection wavelength of 254 nm.
In the chromatogram obtained with solution (2) the area of any peak corresponding to 5-chloro-2- methylaminobenzophenone is not greater than the area of the peak in the chromatogram obtained with solution (1).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Solution (1) contains 0.02% w/v of temazepam BPCRS in methanol (50%). For solution (2) add sufficient methanol (50%) to a weighed quantity of the oral solution containing 20 mg of Temazepam to produce 100 mL.
The chromatographic procedure may be carried out using (a) a stainless steel column (20 cm × 4.6 mm) packed with end- capped octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS is suitable), (b) a mixture of 60 volumes of methanol, 40 volumes of water and 0.03 volumes of diethylamine as the mobile phase with a flow rate of 2 mL per minute and (c) a detection wavelength of 254 nm.
Determine the weight per mL of the oral solution, Appendix V G, and calculate the content of C16H13ClN2O2, weight in volume, using the declared content of C16H13ClN2O2 in temazepam BPCRS.
STORAGE
Temazepam Oral Solution should be protected from light.
