Butalbital, Acetaminophen, and Caffeine Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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Butalbital, Acetaminophen, and Caffeine Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of butalbital (C₁₁H₁₆N₂O₃), Acetaminophen (C₈H₉NO₂), and caffeine (C₈H₁₀N₄O₂).

Packaging and storage-Preserve in tight containers.

1 USP REFERENCE STANDARDS (11)

USP Acetaminophen RS

USP Butalbital RS

USP Caffeine RS

Identification-The retention times of the butalbital, acetaminophen, and caffeine peaks in the chromatogram of the Assay preparation correspond to those of the butalbital, acetaminophen, and caffeine peaks in the chromatogram of the Standard preparation, as obtained in the Assay.

2 DISSOLUTION (711)

Medium: water; 900 mL.

Apparatus 1: 100 rpm.

Time: 60 minutes.

Mobile phase and Chromatographic system-Prepare as directed in the Assay under Butalbital, Acetaminophen, and Caffeine Tablets.

Standard preparation-Prepare a solution in methanol having known concentrations of about 0.024 mg of USP Acetaminophen RS per mL, 0.02B mg of USP Butalbital RS per mL, and 0.02C mg of USP Caffeine RS per mL, in which A, B, and C are the labeled amounts, in mg of acetaminophen, butalbital, and caffeine, respectively, per Capsule. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, dilute with water to volume, and mix.

Procedure-Pass a portion of the solution under test through a filter of 10-µm or finer porosity. Separately inject equal volumes (about 20 µL) of the filtrate and the Standard preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantities, in mg, of butalbital (C₁₁H₁₆N₂O₃), acetaminophen (C₈H₉NO₂), and caffeine (C₈H₁₀N₄O₂) dissolved by the same formula:

900C(r_U/r_S)

in which C is the concentration, in mg per mL, of the appropriate USP Reference Standard in the Standard preparation; and r_U and r_S are the peak responses of the corresponding analyte obtained from the solution under test and the Standard preparation, respectively. Tolerances-Not less than 80% (Q) of the labeled amounts of C₁₁H₁₆N₂O₃, C₈H₉NO₂, and C₈H₁₀N₄O₂ is dissolved in 60 minutes.

UNIFORMITY OF DOSAGE UNITS (905): meet the requirements.

3 Assay

Mobile phase, Internal standard solution, Butalbital standard stock solution, Caffeine standard stock solution, Standard preparation, and Chromatographic system-Proceed as directed in the Assay under Butalbital, Acetaminophen, and Caffeine Tablets.

Assay preparation-Remove, as completely as possible, the contents of not fewer than 20 Capsules. Transfer an accurately weighed portion of the powder, equivalent to about the weight of the contents of 1 Capsule, to a 200-mL volumetric flask, add Internal standard solution to volume, and mix. Sonicate for 15 minutes, mix, and allow to cool and settle. Transfer 20.0 mL of the clear supernatant to a 50-mL volumetric flask, dilute with water to volume, and mix. Pass a portion of this solution through a filter of 0.5 µm or finer porosity, discarding the first 5 mL

of the filtrate. Use the clear filtrate as the Assay preparation. 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 peak responses for the major peaks. Calculate the quantities, in mg, of butalbital (C₁₁H₁₆N₂O₃), acetaminophen (C₈H₉NO₂), and caffeine (C₈H₁₀N₄O₂) in the portion of Capsules taken by the formula:

500D(R_U/R_S)

in which D is the concentration, in mg per mL, of the appropriate USP Reference Standard in the Standard preparation; and R_U and R_S are the peak response ratios of the corresponding analyte to phenacetin obtained from the Assay preparation and the Standard preparation, respectively.