Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Respiratory and central nervous system stimulant.
DEFINITION
Caffeine Citrate Oral Solution is a solution of caffeine citrate, prepared by the interaction of Caffeine and Citric Acid Monohydrate, in a suitable aqueous vehicle. Sodium citrate may also be present.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.
Content of caffeine citrate, C8H10N4O2,C6H8O7
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solution preparing a mixture containing 2 volumes of methanol and 3 volumes of dichloromethane.
(1) Dilute a volume of the oral solution containing the equivalent of 10 mg of caffeine to 100 mL.
(2) 0.01% w/v of caffeine BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel F254.
(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 and examine under ultraviolet light (254 nm).
MOBILE PHASE
1 volume of concentrated ammonia, 3 volumes of acetone, 3 volumes of dichloromethane and 4 volumes of butan-1-ol.
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).
B. In the Assay, the chromatogram obtained with solution (1) shows a principal peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
C. Yields the reaction characteristic of citrates, Appendix VI.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in water.
(1) Dilute a volume of the oral solution containing the equivalent of 50 mg caffeine to 250 mL and filter through a 0.45-µm filter.
(2) Dilute 1 volume of solution (1) to 100 volumes and dilute 1 volume of the resulting solution to 5 volumes.
(3) 0.02% w/v each of theobromine, 1,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione (impurity F), theophylline BPCRS and caffeine BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Waters C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 275 nm.
(f) Inject 10 µL of each solution.
MOBILE PHASE
4 volumes of tetrahydrofuran, 5 volumes of acetonitrile and 191 volumes of 0.01M anhydrous sodium acetate, previously adjusted to pH 4.5 with glacial acetic acid.
SYSTEM SUITABILITY
The test is not valid unless, the chromatogram obtained with solution (3) has 4 distinct peaks and the resolution between the peaks due to theophylline and caffeine is at least 6.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than 0.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in water.
(1) Dilute a volume of the oral solution containing the equivalent of 50 mg caffeine to 250 mL and filter through a 0.45-µm filter.
(2) 0.02% w/v of caffeine BPCRS.
(3) 0.02% w/v each of theobromine, 1,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione, theophylline BPCRS and caffeine BPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, the chromatogram obtained with solution (3) has 4 distinct peaks and the resolution between the peaks due to theophylline and caffeine is at least 6.0.
DETERMINATION OF CONTENT
Calculate the content of C8H10N4O2,C6H8O7 in the oral solution using the declared content of C8H10N4O2 in caffeine BPCRS.
Each mg of C8H10N4O2 is equivalent to 1.989 mg of C8H10N4O2,C6H8O7
LABELLING
The quantity of active ingredient is stated in terms of the amount of caffeine citrate and the equivalent amount of caffeine.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A, B, C, D and F listed under Caffeine.
