Budesonide
Pregna-1,4-diene-3,20-dione, 16,17-butylidenebis(oxy)-11,21-dihydroxy-, [11,16(R)], and 16,17-[(S)-Butylidenebis(oxy)]-11,21-dihydroxypregna-1,4-diene-3,20-dione. (RS)-11,16,17,21-Tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde [51372-29-3; 51372-28-2; 51333-22-3]. » Budesonide is a mixture of two epimeric forms, epimer A(C-22S) and epimer B(C-22R). It contains not less than 44.0 percent and not more than 51.0 percent of epimer A, and the sum of both epimers is not less than 98.0 percent and not more than 102.0 percent of C25H34O6, calculated on the dried basis.
noteProtect all solutions containing budesonide from light.
Packaging and storage
Preserve in tight, light-resistant containers. Store at controlled room temperature.
USP Reference standards 11
USP Budesonide RS.
Identification
A:
Infrared Absorption 197K.
B:
Ultraviolet Absorption 197U
Solution:
25 µg per mL.
Medium:
methanol.
Microbial enumeration tests 61 and Tests for specified microorganisms 62
The total aerobic microbial count does not exceed 1000 cfu per g, and the total combined molds and yeast count does not exceed 100 cfu per g.
Loss on drying 731
Dry it at 105 to constant weight. It loses not more than 0.3% of its weight.
Limit of 21-acetate of budesonide
Buffer solution
Proceed as directed in the Assay.
Mobile phase
Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (55:45). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution
Prepare as directed for the Standard preparation in the Assay.
Test solution
Prepare as directed for the Assay preparation.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 3.1 for the first eluted epimer of 21-acetate of budesonide, about 3.2 for the second eluted epimer of 21-acetate of budesonide, 1.0 for the first eluted epimer of budesonide (epimer B), and about 1.1 for the second eluted epimer of budesonide (epimer A); and the column efficiency is not less than 5500 theoretical plates, determined from the budesonide epimer B peak.
Procedure
Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of the 21-acetate of budesonide in the portion of Budesonide taken by the formula:
100(ri / rS)
in which ri is the sum of the peak areas for the two epimers of the 21-acetate of budesonide; and rS is the sum of the areas of the two budesonide peaks; not more than 0.10% of the 21-acetate of budesonide is found.
Limit of 11-ketobudesonide
Buffer solution
Proceed as directed in the Assay.
Mobile phase
Prepare a filtered and degassed mixture of Buffer solution, acetonitrile, and isopropanol (65:26:9). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution
Prepare as directed for Standard preparation in the Assay.
Test solution
Proceed as directed for the Assay preparation.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains 3.5-µm packing L1. The flow rate is about 1.5 mL per minute. Maintain the column at 50. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.73 and 0.78, respectively, for the two epimers of 11-ketobudesonide, about 0.68 for 21-dehydrobudesonide, about 0.84 for 14,15-dehydrobudesonide, and 1.0 for the first eluted epimer of budesonide (epimer B); the resolution, R, between the first epimer of 11-ketobudesonide and 21-dehydrobudesonide is not less than 1.0 and between the second epimer of 11-ketobudesonide and 14,15-dehydrobudesonide is not less than 1.2; and the column efficiency is not less than 5500 theoretical plates, determined from the budesonide epimer B peak.
Procedure
Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of 11-ketobudesonide in the portion of Budesonide taken by the formula:
100(ri / rU)
in which ri is the sum of the areas of the two ketobudesonide peaks; and rU is the sum of the areas of the two budesonide peaks; not more than 0.2% of 11-ketobudesonide is found.
Related compounds
Buffer solution and Mobile phase
Proceed as directed in the Assay.
Standard solution
Prepare as directed for the Standard preparation in the Assay.
Test solution
Proceed as directed for the Assay preparation.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the column efficiency is not less than 5500 theoretical plates, determined from the budesonide epimer B peak.
Procedure
Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure all of the peak responses. Calculate the percentage of each impurity in the portion of Budesonide taken by the formula:
100(ri / rs)
in which ri is the peak area response for each impurity; and rs is the sum of the responses of all the peaks: the impurities meet the requirements listed in the Table below.
Assay
Buffer solution
Dissolve 3.17 g of monobasic sodium phosphate in water, add 0.23 g of phosphoric acid, dilute with water to 1000 mL, and mix. The pH is 3.2 ± 0.1.
Mobile phase
Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (68:32). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation
Dissolve an accurately weighed quantity of USP Budesonide RS in acetonitrile, and dilute quantitatively, and stepwise if necessary, with Buffer solution to obtain a solution having a known concentration of about 0.5 mg per mL. The proportion of acetonitrile in the Standard preparation does not exceed 30%.
Assay preparation
Transfer about 25 mg of Budesonide, accurately weighed, to a 50-mL volumetric flask, dissolve in 15 mL of acetonitrile, dilute with Buffer solution to volume, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention time for epimer A is 1.1 with respect to epimer B; the resolution, R, between the two budesonide epimer peaks is greater than 1.5; and the column efficiency is not less than 5500 theoretical plates, determined from the budesonide epimer B peak.
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 area responses for the major peaks. Calculate the percentage of epimer A (C25H34O6) in the portion of Budesonide taken by the formula:
100[rUA / (rUA + rUB)]
in which rUA and rUB are the peak area responses for epimer A and epimer B obtained from the Assay preparation, respectively. Calculate the quantity, in mg, of budesonide (C25H34O6) in the portion of Budesonide taken by the formula:
50C[(rUA + rUB) / (rSA + rSB)]
in which C is the concentration, in mg per mL, of USP Budesonide RS in the Standard preparation; rSA and rSB are the peak area responses for epimer A and epimer B obtained from the Standard preparation, respectively; and the other terms are as defined above.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 1714
Pharmacopeial Forum: Volume No. 34(4) Page 907
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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