Dutasteride

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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(5α,17β)-N-[2,5-Bis(triuoromethyl)phenyl]-3-oxo-4-azaandrost-1-ene-17-carboxamide;

α,α,α,α′,α′,α′-Hexauoro-3-oxo-4-aza-5α-androst-1-ene-17β-carboxy-2′,5′-xylidide CAS RN^®: 164656-23-9.

1 DEFINITION

Dutasteride contains NLT 97.0% and NMT 102.0% of dutasteride (C₂₇H₃₀F₆N₂O₂), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 1974, 197K, or 197M

8. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Diluent: Acetonitrile and water (60:40)

Mobile phase: Acetonitrile, water, and trifluoroacetic acid (52:48:0.025)

System suitability solution: 0.5 mg/mL of USP Dutasteride Resolution Mixture RS in Diluent. Sonicate to dissolve

Standard solution: 0.5 mg/mL of USP Dutasteride RS in Diluent. Sonicate to dissolve.

Sample solution: 0.5 mg/mL of Dutasteride in Diluent. Sonicate to dissolve.

Chromatographic system

(See Chromatography (621) System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm x 25-cm; 5-um packing 1

Column temperature: 35°

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 1.5 times the retention time of dutasteride

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 3 for the relative retention times]

Suitability requirements

Resolution: NLT 1.5 between dutasteride 17e epimer and dutasteride, System suitability solution

Relative standard deviation: NMT 1.5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of dutasteride (C₂₇H₃₀F₆N₂O₂) in the portion of Dutasteride taken:

Result = (r_U/(r_S) × (C_S /C_U) × 100

r_U = peak response of dutasteride from the Sample solution

r_S = peak response of dutasteride from the Standard solution

C_S = concentration of USP Dutasteride RS in the Standard solution (mg/mL)

C_U = concentration of Dutasteride in the Sample solution (mg/mL)

Acceptance criteria: 97.0%-102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

RESIDUE ON JOMITION (281): NMT 0.1%

LIMIT OF RESIDUAL SOLVENTS

Standard stock solution: 5 mg/ml, each of acetonitrile, ethyl acetate, pyridine, toluene, dioxane, and n-heptane in dimethyl sulfoxide

Standard solution: 10 µg/mL each of acetonitrile, ethyl acetate, pyridine, toluene, dioxane, and n-heptane in Dimethyl sulfoxide from the Standard stock solution

Sample solution: 10 mg/mL of Dutasteride in dimethyl sulfoxide

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: GC

Detector: Flame ionization

Column: 0.32 - mm *x 30 - m capillary coated with 5-um film of phase G1

Temperatures

Injection port: 180°

Detector: 260°

Column: See Table 1.

Carrier gas: Helium

Flow rate: Head pressure at 12 psi

Split flow: 10 mL/min

Septum purge: 2 mL/min

Injector type: Headspace

Sample volume: 2 mL

Temperatures

Sample: 85°

Needle: 100°

Transfer line: 110°

Times

Equilibration: 1 min

Thermostating: 15 min

System suitability

Sample: Standard solution

Suitability requirements

OFF

Resolution: NLT 1.2 between n-heptane and dioxane peaks

Relative standard deviation: NMT 5% for each solvent

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each solvent in the portion of Dutasteride taken

Result = (r_U/(r_S) × (C_S /C_U) x 100

r_U = peak response of each solvent from the Sample solution

r_S = peak response of each solvent from the Standard solution

C_S = concentration of each solvent in the Standard solution (mg/ml)

C_U = concentration of Dutasteride in the Sample solution (mg/ml)

Acceptance criteria: See Table 2.

ORGANIC IMPURITIES, PROCEDURE 1

Diluent, Mobile phase, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability

Sample: System suitability solution

NOTE-See Table 3 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between dutasteride 17a-epimer and dutasteride

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Dutasteride taken:

Result = (r_U/(r_S) x (1/F) x 100

r_U = peak area for each impurity from the Sample solution

r_S = sum of all the peak areas from the Sample solution

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3

^a (5α,17β)-3-Oxo-4-azaandrost-1-ene-17-carboxylic acid.

^b (5α,17β)-N,N-Dimethyl-3-oxo-4-azaandrost-1-ene-17-carboxamide.

^c Methyl (5α,17β)-3-oxo-4-azaandrost-1-ene-17-carboxylate.

^d Ethyl (5α,17β)-3-oxo-4-azaandrost-1-ene-17-carboxylate.

^e (17α)-N-[2,5-Bis(triuoromethyl)phenyl]-3-oxo-4-azaandrost-1,5(6)-diene-17-carboxamide.

^f (1α,5α,17β)-N-[2,5-Bis(triuoromethyl)phenyl]-1-chloro-3-oxo-4-azaandrostane-17-carboxamide.

^g (17β)-N-[2,5-Bis(triuoromethyl)phenyl]-3-oxo-4-azaandrost-1,5(6)-diene-17-carboxamide.

Change to read:

ORGANIC IMPURITIES, PROCEDURE 2

Diluent, System suitability solution, and Sample solution: Prepare as directed in the Assay.

Mobile phase: Acetonitrile and water (80:20)

Chromatographic system

(See Chromatography (621). System Suitability)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm x 15-cm; 5-um packing L11

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 5 times the retention time of dutasteride

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.5 between dutasteride e-dimer and dutasteride B-dimer peaks

Analysis

Sample: Sample solution

Integrate the dutasteride peak and all drug-related peaks eluting after the dutasteride peak.

Calculate the percentage of each impurity in the portion of Dutasteride taken:

Result = (r_U/(r_S) x (1/F) x 100

r_U = peak area for each impurity from the Sample solution

r_S = sum of all the peak areas from the Sample solution

F = relative response factor (see Table 4)

Acceptance criteria: See Table 4

^a N-(2,5-Bis(trifluoromethyl)phenyl)-3-oxo-4-aza-50-androstane-173-carboxamide

^b Sum of impurities from Table 3 and Table 4

5 SPECIFIC TESTS

WATER DETERMINATION (92.1), Method Methodic

Sample: 100 mg

Analysis: The Sample is heated in a tube at 180° for 4 min in a stream of dry inert gas.

Acceptance criteria

For the anhydrous form: NMT 0.50%

For the hydrate form: NMT 2.0% Water Determination (921), Method Method la may also be used

OPTICAL ROTATION (7815), Procedures. Specific Rotation

Sample solution: 10 mg/ml. in chloroform and alcohol (98:2)

Acceptance criteria: +15.0° to +25.0°

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store below 30°

LABELING: Where it is the hydrate form, the label so indicates.