Edition: BP 2025 (Ph. Eur. 11.6 update)
Diazepam Oral Solution
General Notices
Action and use
Benzodiazepine.
DEFINITION
Diazepam Oral Solution is a solution of Diazepam in a suitable flavoured vehicle.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.
Content of diazepam, C16H13ClN2O
95.0 to 115.0% of the stated amount.
IDENTIFICATION
A. The light absorption, Appendix II B, in the range 320 to 400 nm of the final solution obtained in the Assay exhibits a maximum at 368 nm. The light absorption in the range 230 to 330 nm of a solution prepared by diluting 1 volume of the final solution obtained in the Assay to 5 volumes with 0.1M methanolic sulfuric acid exhibits two maxima, at 243 nm and 286 nm.
B. Carry out the method described under Related substances applying separately to the plate 10 µL of each of solution (1) and solution (2) and using as solution (2) a 0.4% w/v solution of diazepam BPCRS in ethanol (96%). After removal of the plate, allow the solvent to evaporate 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).
TESTS
Acidity
pH, 4.0 to 6.6, Appendix V L.
Related substances
Carry out in subdued light the method for thin-layer chromatography, Appendix III A, using silica gel GF254 as the coating substance and a mixture of equal volumes of ethyl acetate and hexane as the mobile phase but allowing the solvent front to ascend 12 cm above the line of application. Apply separately to the plate 25 µL of each of the following solutions. For solution (1) add 40 mL of water to a volume of the oral solution containing 8 mg of Diazepam and extract with three 50-mL quantities of ether. Wash the combined ether extracts with 30 mL of 1M sodium hydroxide followed by two 40 mL quantities of water. Shake the extract with anhydrous sodium sulfate, filter, evaporate to dryness and dissolve the residue in 2 mL of ethanol (96%). Solution (2) contains 0.0080% w/v of 5-chloro-2-methylaminobenzophenone BPCRS in ethanol (96%). Solution (3) contains 0.0040% w/v of 3-amino-6-chloro-1-methyl-4-phenylquinolin-2-ol BPCRS in ethanol (96%). For solution (4) dilute 2 mL of solution (1) to 100 mL with ethanol (96%) and dilute 1 mL of the resulting solution to 10 mL with the same solvent. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm). In the chromatogram obtained with solution (1) any spot corresponding to 5-chloro-2-methylaminobenzophenone is not more intense than the spot in the chromatogram obtained with solution (2) and any spot corresponding to 3-amino-6-chloro-1- methyl-4-phenylquinolin-2-ol is not more intense than the spot in the chromatogram obtained with solution (3). Any other secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (4).
ASSAY
To a weighed quantity containing 1 mg of Diazepam add 25 mL of a mixture of equal volumes of 1M sodium hydroxide and methanol and shake for 2 minutes. Extract with five 25 mL quantities of chloroform, shaking for 2 minutes each time. Combine the chloroform extracts, shake with 5 g of anhydrous sodium sulfate and filter. Evaporate to dryness, dissolve the residue in 25 mL of 0.1M methanolic sulfuric acid and filter. Measure the absorbance of the filtrate, Appendix II B, at the maximum at 368 nm. Calculate the content of C16H13ClN2O taking 151 as the value of A(1%, 1 cm) at the maximum at 368 nm. Determine the weight per mL of the oral solution, Appendix V G, and calculate the content of C16H13ClN2O, weight in volume.
STORAGE
Diazepam Oral Solution should be protected from light.
