Azathioprine Oral Suspension
» Azathioprine Oral Suspension contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of azathioprine (C9H7N7O2S). Prepare Azathioprine Oral Suspension 50 mg per mL as follows (see Pharmaceutical Compounding—Nonsterile Preparations 795):
Azathioprine 5 g
Vehicle: a mixture of Vehicle for Oral Solution, (regular or sugar-free), NF and Vehicle for Oral Suspension, NF (1:1)
a sufficient quantity to make 100 mL
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.
Packaging and storage— Preserve in tight, light-resistant containers. Store at room temperature, or in a cold place.
Labeling— Label it to state that it is to be well shaken before use, and to state the beyond-use date.
pH 791: between 3.8 and 4.8.
Beyond-use date: 60 days after the day on which it was compounded.
Mobile phase— Dissolve 1.1 g of sodium 1-heptanesulfonate in 700 mL of water, add 300 mL of methanol, and mix. Adjust with 1 N hydrochloric acid to a pH of 3.5. Filter, and degas the solution. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve about 25 mg of USP Azathioprine RS, accurately weighed, in a 50-mL volumetric flask. Add about 15 mL of methanol and 0.5 mL of ammonium hydroxide to the flask, swirl and sonicate for 2 minutes. Dilute with methanol to volume, and mix. Transfer 10 mL of this solution to a 50-mL volumetric flask, dilute with water to volume, and mix.
Assay preparation— Agitate the container of Oral Suspension for 30 minutes 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 seconds. Pipet 1.0 mL of the sample solution into a 100-mL volumetric flask, and dilute with Mobile phase to volume.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm analytical column that contains 5-µm packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the retention time is about 4 minutes, and the relative standard deviation for replicate injections is not more than 1.3%.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of azathioprine (C9H7N7O2S) in the volume of Oral Suspension taken by the formula:
100(C / V)(rU / rS)
in which C is the concentration, in µg per mL, of USP Azathioprine RS in the Standard preparation; V is the volume, in mL, of Oral Suspension taken; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Rick G. Schnatz
Manager, Compounding Pharmacy Expert Committee
(CRX05) Compounding Pharmacy05
Reference Standards Lili Wang, Technical Services Scientist
USP32–NF27 Page 1611
Pharmacopeial Forum: Volume No. 32(1) Page 48