Ergotamine Tartrate and Caffeine Suppositories

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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1 DEFINITION

Ergotamine Tartrate and Caffeine Suppositories contain NLT 90.0% and NMT 110.0% of the labeled amounts of ergotamine tartrate [(C₃₃H₃₅N₅O₅)₂ · C₄H₆O₆] and caffeine (C₈H₁₀N₄O₂).

2 IDENTIFICATION

A.

Solution A: 10 mg/mL of tartaric acid in water

Sample solution: Melt 1 Suppository in 10 mL of hot Solution A. Chill the mixture until the layer of oil has hardened, then filter, divide the filtrate into two parts, and use one part. Reserve the other part of this filtrate for use in Identification test B.

Analysis

Sample: Sample solution

To one portion of the Sample solution, add 10 mL of p-dimethylaminobenzaldehyde TS.

Acceptance criteria: A blue color develops (presence of ergotamine).

B.

Sample solution: Use the remaining portion of the Sample solution from Identification test A.

Analysis

Sample: Sample solution

Transfer the Sample solution to a small evaporating dish, and evaporate to dryness on a steam bath. Add 1 mL of hydrochloric acid and 100 mg of potassium chlorate, and evaporate. Invert the dish over a vessel containing ammonium hydroxide.

Acceptance criteria: The residue acquires a purple color, which disappears upon the addition of 1 N sodium hydroxide (presence of caffeine).

3 ASSAY

PROCEDURE

Protect all solutions from light.

Solution A: Acetonitrile, water, and triethylamine (150:850:0.5) adjusted by the dropwise addition of fluorometric grade sulfuric acid to a pH of 3.1 ± 0.1

Solution B: Acetonitrile, water, and triethylamine (620:1380:1) adjusted by the dropwise addition of fluorometric grade sulfuric acid to a pH of 3.1 ± 0.1. Make any necessary adjustments in pH to meet relative retention times, and make other adjustments if necessary.

Solution C: 10 mg/mL of tartaric acid in water

Mobile phase: See Table 1.

Table 1

^a Do not switch to using 100% of Solution B until 3 min after the injection of a sample or until after the caffeine peak has eluted, whichever occurs last.

Diluent: Methanol and Solution C (50:50)

Standard stock solution: 40 µg/mL of USP Ergotamine Tartrate RS in Diluent

Standard solution: 20 µg/mL of USP Ergotamine Tartrate RS from Standard stock solution and 1 mg/mL of USP Caffeine RS in Diluent

System suitability solution: 10 µg/mL of USP Ergotamine Tartrate RS and 0.5 mg/mL of USP Caffeine RS from Standard solution and 2 µg/mL of USP Ergotaminine RS in Diluent

Sample solution: Nominally 20 µg/mL of ergotamine tartrate from NLT 20 Suppositories prepared as follows. Weigh NLT 20 Suppositories, and grind to a fine mesh. Transfer a portion of the ground mass, equivalent to 2 mg of ergotamine tartrate, to a suitable glass-stoppered flask. Add 100.0 mL of Diluent, insert the stopper in the flask, and place it in a water bath maintained at 40°. Shake vigorously for 5 min, or longer if necessary, until the specimen is completely melted. Sonicate for 30 min, and transfer to a freezer for 45 min. Pass through a glass fiber filter of 0.7-µm pore size, and discard the first 5-10 mL of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 244 nm (for caffeine), in series with a fluorometric detector (for ergotamine tartrate) with excitation at 229 nm and detection at 435 nm

Column: 4.6-mm x 25-cm; packing L7

Flow rate: 2 mL/min

Injection volume: 10 µL

System suitability

Samples: Standard solution and System suitability solution

[NOTE-The relative retention times for caffeine, ergotamine, and ergotaminine are 1.0, 4, and 4.5, respectively.]

Suitability requirements

Resolution: NLT 3.0 between ergotamine and ergotaminine, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of caffeine (C₈H₁₀N₄O₂) in the portion of Suppositories taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of caffeine from the Sample solution

r_s = peak response of caffeine from the Standard solution

C_s = concentration of USP Caffeine RS in the Standard solution (mg/mL)

C_u = nominal concentration of caffeine in the Sample solution (mg/mL)

Calculate the percentage of the labeled amount of ergotamine tartrate [(C₃₃H₃₅N₅O₅)₂ · C₄H₆O₆] in the portion of Suppositories taken:

Result = (I_u /I_s ) × (C_s /C_u ) × 100

I_u = uorometric response of ergotamine from the Sample solution

I_s = uorometric response of ergotamine from the Standard solution

C_s = concentration of USP Ergotamine Tartrate RS in the Standard solution (µg/mL)

C_u = nominal concentration of ergotamine tartrate in the Sample solution (µg/mL)

Acceptance criteria: 90.0%–110.0% of the labeled amounts of ergotamine tartrate [(C₃₃H₃₅N₅O₅)₂ · C₄H₆O₆] and caffeine (C₈H₁₀N₄O₂).

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, at a temperature not above 25°. Do not expose unwrapped Suppositories to sunlight.

USP Reference Standards 〈11〉

USP Caffeine RS

USP Ergotamine Tartrate RS

USP Ergotaminine RS