Caffeine Citrate Injection
» Caffeine Citrate Injection is a sterile solution containing Caffeine and citric acid in Water for Injection. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of caffeine citrate (C14H18N4O9). It contains no bacteriostat or other preservative.
Packaging and storage Preserve in single-dose, tight containers of Type I glass, and store at a temperature between 15 and 30.
USP Reference standards 11
USP Endotoxin RS
A: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
B: It meets the requirements of the test for Citrate 191.
C: Transfer about 4 g of potassium iodide to a 100-mL volumetric flask. Add 10 mL of water, and shake until the potassium iodide is dissolved. Transfer 2 g of iodine to the volumetric flask, and shake until dissolved. Dilute with water to volume, and mix. Transfer 5 drops of the solution so obtained to a 25-mL centrifuge tube containing 5.0 mL of the Injection, and mix. Add 0.5 mL of 2.0 M hydrochloric acid solution, and mix: a brown precipitate that dissolves on neutralization with 0.5 mL of sodium hydroxide TS is produced.
Color and clarity Transfer a suitable portion of the Injection to a clear glass test tube, and visually examine the solution in a well-lighted area: the solution is colorless and free of haze, obvious turbidity, and precipitate.
Bacterial endotoxins 85: not more than 0.25 USP Endotoxin Unit per mg of caffeine.
Sterility 71 It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined.
pH 791: between 4.2 and 5.2.
Particulate matter 788: not more than 150 particles are equal to or greater than 10 µm, and not more than 25 particles are equal to or greater than 25 µm.
Mobile phase and Theophylline solution Proceed as directed in the Assay.
Standard solution Use the Standard preparation, prepared as directed in the Assay.
System sensitivity solution Transfer 2.5 mL of the Standard solution to a 100-mL volumetric flask, dilute with water to volume, and mix.
Test solution Use the Assay preparation, prepared as directed in the Assay.
Chromatographic system (see Chromatography 621) Proceed as directed in the Assay. Chromatograph the System sensitivity solution, and record the peak responses as directed for Procedure: the theophylline peak produces a discernible peak response at its retention time.
Procedure Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of any related compound in the portion of Injection taken by the formula:
100F(386.31/194.19)(CS / CW)(ri / rS)in which F is the relative response factor and is equal to 0.878 for theobromine at a relative retention time of about 0.4, equal to 1.10 for paraxanthine at a relative retention time of about 0.6, equal to 0.905 for theophylline at a relative retention time of about 0.7, and equal to 1.0 for any other related compound; 386.31 and 194.19 are the molecular weights of caffeine citrate and caffeine, respectively; CS is the concentration, in mg per mL, of USP Caffeine RS in the Standard solution; CW is the caffeine citrate concentration, in mg per mL, in the Test solution, as obtained in the Assay; ri is the individual peak response for each related compound obtained from the Test solution; and rS is the caffeine peak response obtained from the Standard solution: not more than 0.10% of any individual related compound is found; and not more than 0.1% of total impurities is found.
Other requirements It meets the requirements under Injections 1.
Mobile phase Prepare a mixture of 0.01 M sodium acetate, acetonitrile, and tetrahydrofuran (191:5:4). Adjust with glacial acetic acid to a pH of 4.5, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Theophylline solution Dissolve an accurately weighed quantity of theophylline in water, and dilute quantitatively, and stepwise if necessary, with water, to obtain a solution having a concentration of about 0.02 mg per mL.
Standard preparation Transfer about 5 mg of USP Caffeine RS, accurately weighed, to a 25-mL volumetric flask. Add 5 mL of Theophylline solution, dissolve in and dilute with water to volume, and mix.
Assay preparation Transfer an accurately measured volume of Injection, equivalent to about 50 mg of caffeine, to a 250-mL volumetric flask. Dilute with water to volume, mix, and pass through a polyvinylidene difluoride or equivalent membrane having a 0.45-µm porosity.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 275-nm detector and a 4.6-mm × 150-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for theophylline and 1.0 for caffeine; the resolution, R, between theophylline and caffeine is not less than 6.0; the tailing factor, determined from the theophylline and caffeine peaks, is not more than 2.0; and the relative standard deviation for replicate injections, determined from the caffeine peaks, is not more than 2.0%.
Procedure Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the caffeine peak responses. Calculate the quantity, in mg, of caffeine citrate (C14H18N4O9) in the volume of Injection taken by the formula:
250(386.31/194.19)C(rU / rS)in which 386.31 and 194.19 are the molecular weights of caffeine citrate and caffeine, respectively; C is the concentration, in mg per mL, of USP Caffeine RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2428Pharmacopeial Forum: Volume No. 30(5) Page 1590