Azathioprine Compounded Oral Suspension

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Azathioprine Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of azathioprine (C₉H₇N₇O₂S).

Prepare Azathioprine Compounded Oral Suspension 50 mg/mL as follows (see Pharmaceutical Compounding-Nonsterile Preparations (795)).

If using tablets, comminute them to a fine powder in a suitable mortar, or add Azathioprine powder to the mortar. Add about 10 mL of the Vehicle, and mix to a uniform paste. Add the Vehicle in small portions almost to volume, and mix thoroughly after each addition. Transfer the contents of the mortar, stepwise and quantitatively, to a calibrated bottle. Add sufficient Vehicle to bring to final volume, and mix well.

[CAUTION-Avoid skin contact or inhalation of azathioprine by using protective gloves and a fume hood or surgical mask.]

2 ASSAY

2.1 PROCEDURE

Mobile phase: Dissolve 1.1 g of sodium-1-heptanesulfonate in 700 mL of water, and add 300 mL of methanol. Adjust with 1 N hydrochloric acid to a pH of 3.5.

Standard solution: Transfer 25 mg of USP Azathioprine RS to a 50-mL volumetric flask. Add 15 mL of methanol and 0.5 mL of ammonium hydroxide to the flask, swirl, and sonicate for 2 min. Dilute with methanol to volume. Transfer 10 mL of this solution to a 50-mL volumetric flask, and dilute with water to volume.

Sample solution: Agitate the container of Oral Suspension for 30 min on a rotating mixer, remove a 5-mL sample, and store in a clear glass vial at -70° until analyzed. At the time of analysis, remove the sample from the freezer, allow it to reach room temperature, and mix with a vortex mixer for 30 s. Pipet 1.0 mL of the sample into a 100-mL volumetric flask, and dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 2 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[NOTE-The retention time for the azathioprine peak is about 4 min.]

Suitability requirements

Relative standard deviation: NMT 1.3% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of azathioprine (C₉H₇N₇O₂S) in the portion of Oral Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution 

C_S = concentration of USP Azathioprine RS in the Standard solution (mg/mL)

C_U = nominal concentration of azathioprine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

3 SPECIFIC TESTS

PH (791): 3.8-4.8

4 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Package in tight, light-resistant containers. Store at room temperature, or in a refrigerator.

BEYOND-USE DATE: NMT 60 days after the day on which it was compounded when stored at room temperature, or in a refrigerator

LABELING: Label it to state that it is to be well shaken before use, and to state the Beyond-Use Date.

USP REFERENCE STANDARDS (11)

USP Azathioprine RS