Printed on: Fri Jan 05 2024, 09:36:57 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-DF0642F1-C2DE-46C1-B7E3-AB4967A4DF50_4_en-US

Printed by: USP NF Official Date: Official as of 01-May-2020 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: e8wfe DOI: https://doi.org/10.31003/USPNF_M43990_04_01
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Suitability requirements
Ketoconazole 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 = (r U/r S) × (C S/C U) × 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)
C26H28Cl2N4O4 531.43
Piperazine, 1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H- Acceptance criteria: 98.0%–102.0% on the dried basis
imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-,
cis-; IMPURITIES
(±)-cis-1-Acetyl-4-(p-[[2-(2,4-dichlorophenyl)-2-(imidazol-1- • RESIDUE ON IGNITION á281ñ
ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl)piperazine Sample: 2 g
CAS RN®: 65277-42-1; UNII: R9400W927I. Acceptance criteria: NMT 0.1%

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• ORGANIC IMPURITIES
DEFINITION Buffer, Solution A, Solution B, Mobile phase, Diluent, and
Ketoconazole contains NLT 98.0% and NMT 102.0% of Chromatographic system: Proceed as directed in the
ketoconazole (C26H28Cl2N4O4), calculated on the dried basis. Assay.
ci Standard solution: 0.01 mg/mL each of USP Ketoconazole
IDENTIFICATION RS and USP Terconazole RS in Diluent
Change to read: Sample solution 10.0 mg/mL of Ketoconazole in Diluent
System suitability
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared Sample: Standard solution
Spectroscopy: 197K▲ (CN 1-May-2020) Suitability requirements
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• B. The retention time of the major peak of the Sample Resolution: NLT 2.0 between ketoconazole and
solution corresponds to that of the Standard solution, as terconazole peaks
obtained in the Assay. Relative standard deviation: NMT 5.0% for the
ketoconazole peak
ASSAY Analysis
• PROCEDURE Samples: Standard solution and Sample solution
Buffer: 3.4 mg/mL of tetrabutyl ammonium hydrogen
O

Calculate the percentage of any impurities in the portion of

sulfate in water Ketoconazole taken:
Solution A: Acetonitrile and Buffer (5:95)
Solution B: Acetonitrile and Buffer (50:50) Result = (r U/r S) × (C S/C U) × 100
Mobile phase: See Table 1.
rU = peak response of any impurities from the
Table 1 Sample solution
Time Solution A Solution B rS = peak response of Ketoconazole from the Standard
(min) (%) (%) solution
0 100 0
CS = concentration of USP Ketoconazole RS in the
Standard solution (mg/mL)
20 0 100 CU = concentration of Ketoconazole in the Sample
25 0 100 solution (mg/mL)
26 100 0 Acceptance criteria: Disregard any peak less than 0.05%.
30 100 0 Any individual unspecified impurity: NMT 0.10%
Total impurities: NMT 2.0%
Diluent: Methanol SPECIFIC TESTS
Standard solution: 0.1 mg/mL of USP Ketoconazole RS in • OPTICAL ROTATION, Specific Rotation á781Sñ
Diluent Sample solution: 40 mg/mL in methanol
Sample solution: 0.1 mg/mL of Ketoconazole in Diluent Acceptance criteria: −1° to +1° at 20°
Chromatographic system • LOSS ON DRYING á731ñ
(See Chromatography á621ñ, System Suitability.) Analysis: Dry under vacuum at 80° for 4 h.
Mode: LC Acceptance criteria: NMT 0.5%
Detector: UV 225 nm
ADDITIONAL REQUIREMENTS
Column: 4.6-mm × 10-cm; 3-µm packing L1
• PACKAGING AND STORAGE: Preserve in well-closed
Flow rate: 2.0 mL/min
containers.
Injection volume: 10 µL
• USP REFERENCE STANDARDS á11ñ
System suitability
USP Ketoconazole RS
Sample: Standard solution

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Printed on: Fri Jan 05 2024, 09:36:57 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-DF0642F1-C2DE-46C1-B7E3-AB4967A4DF50_4_en-US
Printed by: USP NF Official Date: Official as of 01-May-2020 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: e8wfe DOI: https://doi.org/10.31003/USPNF_M43990_04_01
2

USP Terconazole RS cis-1-(p-{[2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-

Piperazine, 1-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4- ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-
triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]- isopropylpiperazine.
4-(1-methylethyl)-, cis-; C26H31Cl2N5O3 532.46

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