11/3/2020 USP-NF Ketoconazole
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O cial Status: Currently O cial on 03-Nov-2020
O cial Date: O cial as of 1-May-2020
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© 2020 USPC
Ketoconazole
C26H28Cl2N4O4 531.43
Piperazine, 1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, cis-;
(±)-cis-1-Acetyl-4-(p-[[2-(2,4-dichlorophenyl)-2-(imidazol-1- ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl)piperazine [65277-42-1]; UNII:
R9400W927I.
DEFINITION
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Ketoconazole contains NLT 98.0% and NMT 102.0% of ketoconazole (C26H28Cl2N4O4), calculated on the dried basis.
IDENTIFICATION
Change to read:
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉, Infrared Spectroscopy: 197K▲ (CN 1-MAY-2020)
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• B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• PROCEDURE
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Buffer: 3.4 mg/mL of tetrabutyl ammonium hydrogen sulfate in water
Solution A: Acetonitrile and Buffer (5:95)
Solution B: Acetonitrile and Buffer (50:50)
Mobile phase: See Table 1.
Table 1
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Time (min) Solution A (%) Solution B (%)
0 100 0
20 0 100
25 0 100
26 100 0
30 100 0
Diluent: Methanol
Standard solution: 0.1 mg/mL of USP Ketoconazole RS in Diluent
Sample solution: 0.1 mg/mL of Ketoconazole in Diluent
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
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11/3/2020 USP-NF Ketoconazole
Mode: LC
Detector: UV 225 nm
Column: 4.6-mm × 10-cm; 3-µm packing L1
Flow rate: 2.0 mL/min
Injection volume: 10 µL
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 0.73%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of ketoconazole (C26H28Cl2N4O4) in the portion of Ketoconazole taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Ketoconazole RS in the Standard solution (mg/mL)
CU = concentration of Ketoconazole in the Sample solution (mg/mL)
Acceptance criteria: 98.0%–102.0% on the dried basis
IMPURITIES
• RESIDUE ON IGNITION 〈281〉
Sample: 2 g
Acceptance criteria: NMT 0.1%
• ORGANIC IMPURITIES
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Buffer, Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.
Standard solution: 0.01 mg/mL each of USP Ketoconazole RS and USP Terconazole RS in Diluent
Sample solution 10.0 mg/mL of Ketoconazole in Diluent
System suitability
Sample: Standard solution
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Suitability requirements
Resolution: NLT 2.0 between ketoconazole and terconazole peaks
Relative standard deviation: NMT 5.0% for the ketoconazole peak
Analysis
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Samples: Standard solution and Sample solution
Calculate the percentage of any impurities in the portion of Ketoconazole taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of any impurities from the Sample solution
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rS = peak response of Ketoconazole from the Standard solution
CS = concentration of USP Ketoconazole RS in the Standard solution (mg/mL)
CU = concentration of Ketoconazole in the Sample solution (mg/mL)
Acceptance criteria: Disregard any peak less than 0.05%.
Any individual unspeci ed impurity: NMT 0.10%
Total impurities: NMT 2.0%
SPECIFIC TESTS
• OPTICAL ROTATION, Specific Rotation 〈781S〉
Sample solution: 40 mg/mL in methanol
Acceptance criteria: −1° to +1° at 20°
• LOSS ON DRYING 〈731〉
Analysis: Dry under vacuum at 80° for 4 h.
Acceptance criteria: NMT 0.5%
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in well-closed containers.
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11/3/2020 USP-NF Ketoconazole
• USP REFERENCE STANDARDS 〈11〉
USP Ketoconazole RS
USP Terconazole RS
Piperazine, 1-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-(1-methylethyl)-, cis-;
cis-1-(p-{[2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-isopropylpiperazine.
C26H31Cl2N5O3 532.46
Auxiliary Information- Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
KETOCONAZOLE Shankari Shivaprasad SM12020 Small Molecules 1
Senior Scienti c Liaison
Chromatographic Database Information: Chromatographic Database
Most Recently Appeared In:
Pharmacopeial Forum: Volume No. 40(4)
Page Information:
USP43-NF38 - 2506
USP42-NF37 - 2454
USP41-NF36 - 2309
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