Printed on: Fri May 19 2023, 05:02:51 AM(EST) Status: Currently Official on 19-May-2023 DocId: GUID-B7FB3C95-EF4F-4A31-9E6F-F30F203DF3E6_1_en-US
Printed by: Anandkumar Joshi Official Date: Official Prior to 2013 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: uze93 DOI: [Link]
1
rS = peak response from the Standard solution
Caffeine Citrate Oral Solution CS = concentration of USP Caffeine RS in the Standard
DEFINITION solution (mg/mL)
Caffeine Citrate Oral Solution is a sterile aqueous solution Mr1 = molecular weight of caffeine citrate, 386.31
containing Caffeine and citric acid. It contains NLT 90.0% Mr2 = molecular weight of caffeine, 194.19
and NMT 110.0% of the labeled amount of caffeine citrate
(C14H18N4O9). It contains no bacteriostat or other Calculate the percentage of the labeled amount of caffeine
preservative. citrate (C14H18N4O9) in the portion of Oral Solution taken:
IDENTIFICATION Result = (CA/CU) × 100
• A. The retention time of the major peak of the Sample
solution corresponds to that of the Standard solution, as CA = concentration of caffeine citrate in the Sample
obtained in the Assay. solution
• B. IDENTIFICATION TESTS—GENERAL, Citrate á191ñ: Meets CU = nominal concentration of caffeine citrate in the
the requirements Sample solution
• C.
Solution A: Transfer 4 g of potassium iodide to a 100-mL Acceptance criteria: 90.0%–110.0%
volumetric flask, and add 10 mL of water. Shake until the
potassium iodide is dissolved. Add 2 g of iodine to the IMPURITIES
volumetric flask, and shake until dissolved. Dilute with • ORGANIC IMPURITIES
water to volume. Mobile phase, Theophylline stock solution, Standard
Sample solution: 5.0 mL of Oral Solution solution, Sample solution, and Chromatographic
system: Proceed as directed in the Assay.
al
Analysis: Transfer the Sample solution to a 25-mL centrifuge
tube, and add 5 drops of Solution A. Add 0.5 mL of 2.0 M Sensitivity solution: 5 µg/mL of caffeine and 0.1 µg/mL of
hydrochloric acid. theophylline from the Standard solution in water
Acceptance criteria: A brown precipitate that dissolves on System suitability
neutralization with 0.5 mL of sodium hydroxide TS is Sample: Sensitivity solution
produced. Suitability requirements
ASSAY
• PROCEDURE
ci Sensitivity: The theophylline peak is discernible.
Analysis
Samples: Standard solution and Sample solution
Mobile phase: Acetonitrile, tetrahydrofuran, and 0.01 M Calculate the percentage of each impurity in the portion of
sodium acetate (5:4:191) adjusted with glacial acetic acid Oral Solution taken:
ffi
to a pH of 4.5
Theophylline stock solution: 0.02 mg/mL of theophylline Result = (rU/rS) × (CS/CA) × (Mr1/Mr2) × (1/F) × 100
in water
Standard solution: 0.2 mg/mL of USP Caffeine RS and rU = peak response of each impurity from the Sample
0.004 mg/mL of theophylline from Theophylline stock solution
solution in water rS = peak response of caffeine from the Standard
O
Sample solution: Nominally 0.4 mg/mL of caffeine citrate solution
(equivalent to 0.2 mg/mL of caffeine) from Oral Solution in CS = concentration of USP Caffeine RS in the Standard
water prepared as follows. Transfer a volume of Oral solution (mg/mL)
Solution, equivalent to 50 mg of caffeine, to a 250-mL CA = concentration of caffeine citrate in the Sample
volumetric flask. Dilute with water to volume, pass solution as determined in the Assay
through a polyvinylidene difluoride or equivalent Mr1 = molecular weight of caffeine citrate, 386.31
membrane of 0.45-µm pore size, and use the filtrate. Mr2 = molecular weight of caffeine, 194.19
Chromatographic system F = relative response factor, (see Table 1)
(See Chromatography á621ñ, System Suitability.)
Mode: LC Acceptance criteria: See Table 1.
Detector: UV 275 nm
Column: 4.6-mm × 15-cm; 5-µm packing L1 Table 1
Flow rate: 1 mL/min Relative Relative Acceptance
Injection volume: 10 µL Retention Response Criteria,
System suitability Name Time Factor NMT (%)
Sample: Standard solution Theobromine 0.4 1.13 0.10
[NOTE—See Table 1 for the relative retention times.]
Suitability requirements Paraxanthine 0.6 0.909 0.10
Resolution: NLT 6.0 between theophylline and caffeine Theophylline 0.7 1.10 0.10
Tailing factor: NMT 2.0 each for the theophylline and
caffeine Caffeine 1.0 — —
Relative standard deviation: NMT 2.0% for caffeine Any individual
—
Analysis impurity 1.0 0.10
Samples: Standard solution and Sample solution Total impurities — — 0.1
Calculate the concentration (CA), in mg/mL, of caffeine
citrate in the Sample solution:
SPECIFIC TESTS
Result = (rU/rS) × CS × (Mr1/Mr2) • STERILITY TESTS á71ñ: It meets the requirements of the Test
for Sterility of the Product to Be Examined, Membrane
rU = peak response from the Sample solution Filtration.
• PH á791ñ: 4.2–5.2
[Link] 1/2
Printed on: Fri May 19 2023, 05:02:51 AM(EST) Status: Currently Official on 19-May-2023 DocId: GUID-B7FB3C95-EF4F-4A31-9E6F-F30F203DF3E6_1_en-US
Printed by: Anandkumar Joshi Official Date: Official Prior to 2013 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: uze93 DOI: [Link]
2
ADDITIONAL REQUIREMENTS • USP REFERENCE STANDARDS á11ñ
• PACKAGING AND STORAGE: Preserve in single-dose, tight USP Caffeine RS
containers, and store at a temperature between 15°–30°.
al
ci
ffi
O
[Link] 2/2