Ursodiol Tablets
DEFINITION
Ursodiol Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of ursodiol (C24H40O4).
IDENTIFICATION
• Thin-Layer Chromatography
Standard solution:
1 mg/mL of USP Ursodiol RS in methanol
Sample solution:
Transfer a quantity of finely powdered Tablets, equivalent to about 25 mg of ursodiol, to a conical flask. Add 25.0 mL of methanol, and mix for 20 min. Centrifuge this solution for 10 min at 4000 rpm, and use the clear supernatant.
Chromatographic system
Mode:
TLC
Adsorbent:
0.25-mm layer of chromatographic silica gel mixture activated for at least 4 h at 105
Application volume:
25 µL
Developing solvent system:
Chloroform, acetone, and acetic acid (7:2:1)
Spray reagent:
Dissolve 2.5 g of phosphomolybdic acid in 50 mL of glacial acetic acid. Add 2.5 mL of concentrated sulfuric acid, and mix well.
Analysis:
Proceed as directed for Chromatography 
621
, Thin-Layer Chromatography. Allow the chromatogram to develop until the solvent front has moved about three-fourths of the length of the plate. Spray the plate lightly with Spray reagent. Dry the plate by heating at 105 for about 7 min.
621, Thin-Layer Chromatography. Allow the chromatogram to develop until the solvent front has moved about three-fourths of the length of the plate. Spray the plate lightly with Spray reagent. Dry the plate by heating at 105 for about 7 min.
Acceptance criteria:
The principal indigo-colored spot of the Sample solution corresponds in color and in RF value to that of the Standard solution.
ASSAY
• Procedure
Mobile phase:
Methanol, water, and phosphoric acid (77:23:0.6)
Internal standard solution:
3.75 mg/mL of propylparaben in Mobile phase
Standard solution:
3.75 mg/mL of USP Ursodiol RS in Internal standard solution
Sample solution:
Weigh and finely powder 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 37.5 mg of ursodiol, to a glass-stoppered conical flask. Add 10.0 mL of Internal standard solution, and shake by mechanical means for 15 min. Sonicate at 40 for an additional 15 min, and filter.
for an additional 15 min, and filter.
Chromatographic system
Mode:
LC
Detector:
Differential refractive index
Detector temperature:
40
Column:
4.6-mm × 25-cm; packing L7
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
[Note—The relative retention times for propylparaben and ursodiol are 0.73 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 3.0 between ursodiol and propylparaben
Column efficiency:
NLT 1600 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C24H40O4 in the portion of Tablets taken:
Result = (RU/RS) × (CS/CU) × 100
| RU | = | = ratio of peak responses from the Sample solution |
| RS | = | = ratio of peak responses from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| CU | = | = nominal concentration of the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
Simulated intestinal fluid TS, prepared without pancreatin and adjusted with 0.1 N sodium hydroxide or 0.1 N hydrochloric acid to a pH of 8.0; 900 mL
Apparatus 2:
75 rpm
Time:
45 min
Mobile phase:
Methanol, water, and phosphoric acid (77:23:0.6)
Sample solution:
Pass a portion of the solution under test through a suitable filter.
Standard solution:
USP Ursodiol RS in Medium
Chromatographic system
Mode:
LC
Detector:
Differential refractive index
Detector temperature:
40
Column:
4.6-mm × 25-cm; packing L7
Flow rate:
1 mL/min
Injection size:
25 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 1600 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Tolerances:
NLT 80% (Q) of the labeled amount of C24H40O4 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Standard solution A:
20 µg/mL of USP Ursodiol RS in methanol
Standard solution B:
10 µg/mL of lithocholic acid in methanol
Standard solution C:
300 µg/mL of chenodeoxycholic acid in methanol
Sample solution:
Transfer a quantity of finely powdered Tablets, equivalent to about 25 mg of ursodiol, to a conical flask. Add 25.0 mL of methanol, and mix for 20 min. Centrifuge this solution for 10 min at 4000 rpm, and use the clear supernatant.
Chromatographic system
Mode:
TLC
Adsorbent:
0.25-mm layer of chromatographic silica gel mixture, activated for at least 4 h at 105
Application volume:
25 µL of Standard solutions A, B, and C; 50 µL of the Sample solution
Developing solvent system:
Chloroform, acetone, and acetic acid (7:2:1)
Spray reagent:
Dissolve 2.5 g of phosphomolybdic acid in 50 mL of glacial acetic acid. Add 2.5 mL of concentrated sulfuric acid, and mix well.
Analysis:
Proceed as directed for Chromatography 621, Thin-Layer Chromatography. Spray the plate lightly with Spray reagent. Dry the plate by heating at 105 for about 7 min.
621, Thin-Layer Chromatography. Spray the plate lightly with Spray reagent. Dry the plate by heating at 105 for about 7 min.
Acceptance criteria:
The spot due to lithocholic acid from the Sample solution, if present, is not greater in size and intensity than that from Standard solution B (0.05%). The spot due to chenodeoxycholic acid from the Sample solution, if present, is not greater in size and intensity than that from Standard solution C (1.5%). No other unidentified spot in the Sample solution is greater in size and intensity than the spot from Standard solution A (0.1%).
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at a temperature between 20 and 25.
and 25.
• USP Reference Standards 11
11
USP Ursodiol RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Elena Gonikberg, Ph.D.
Principal Scientific Liaison 1-301-816-8251 |
(SM32010) Monographs - Small Molecules 3 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4981
Pharmacopeial Forum: Volume No. 35(4) Page 876