Duloxetine Hydrochloride

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

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

DOWNLOAD PDF HERE

2-Thiophenepropanamine, N-methyl-γ-(1-naphthalenyloxy)-, hydrochloride, (S)-;

(+)-(S)-N-Methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine hydrochloride CAS RN^®: 136434-34-9; UNII: 9044SC542W.

1 DEFINITION

Duloxetine Hydrochloride contains NLT 97.0% and NMT 102.0% of duloxetine hydrochloride (C₁₈H₁₉NOS · HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

B. The retention time of the major peak of the Sample solution corresponds to that of the duloxetine S-isomer from the System suitability solution in the test for Limit of Duloxetine Related Compound A.

C. IDENTIFICATION TESTS GENERAL, Chloride (191)

Sample solution: 5 mg/mL in methanol

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDORE

Protect solutions of duloxetine from light.

Buffer: 2.9 g/L of phosphoric acid in water. Adjust with sodium hydroxide solution to a pH of 2.5. To each L of this solution add 10.3 g of sodium 1-hexanesulfonate monohydrate, and dissolve..

Mobile phase: Acetonitrile, n-propanol, and Buffer (13:17:70)

Diluent: Acetonitrile and water (25:75)

System suitability solution: 0.2 mg/ml. of USP Duloxetine Hydrochloride RS (contains duloxetine related compound F) in Mobile phase, Heat the solution to at least 40 for a minimum of 1 h. [Note-The resulting solution contains duloxetine alcohol, duloxetine 4-naphthyl isomer, a naphthol, duloxetine B-naphthol-1-yl isomer, and duloxetine related compound F.

Standard solution: 0.1 mg/mL of USP Duloxetine Hydrochloride RS in Diluent

Sample solution: 0.1 mg/mL of Duloxetine Hydrochloride in Diluent

Chromatographic system

(See Chromatography (621). System Suitability)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm x 15-cm; 3.5µm packing L7

Column temperature: 40:3°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: 2 times the retention time of duloxetine

System suitability

Sample: System suitability solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between duloxetine and duloxetine related compound F

Tailing factor: NMT 1.5 for duloxetine

Relative standard deviation: NMT 1.0% for duloxetine

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of duloxetine hydrochloride (C, H, NOS HCI) in the portion of sample taken:

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

r_U = peak response the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 97.0%~102.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITюм (281): NMT 0.2%

ORGANIC INFURITIES

Protect solutions of duloxetine from light.

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

Sensitivity solution: 0.2 µg/mL of USP Duloxetine Hydrochloride RS in Diluent

Sample solution: 0.2 mg/mL of Duloxetine Hydrochloride in Diluent

Chromatographic system: Proceed as directed in the Assay, except for Run time.

Run time: 2.4 times the retention time of duloxetine

System suitability

Samples: System suitability solution and Sensitivity solution

[NOTE See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between duloxetine 4-naphthyl isomer and a-naphthol; NLT 1.5 between duloxetine and duloxetine related compound

F. System suitability solution

Tailing factor: NMT 1.5 for duloxetine, System suitability solution

Relative standard deviation: NMT 1.0% for duloxetine, System suitability solution

Signal-to-noise ratio: NLT 20 for the duloxetine peak, Sensitivity solution

Analysis

Sample: Sample solution

Calculate the percentage of any individual impurity in the portion of Duloxetine Hydrochloride 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 1)

^a 3-(Methylamino) 1 (thiophen-2-yl)propan-1-ol

^b 4-(3-(Methylamino)-1-(thiophen-2-yl)propyljnaphthalen-1-ol

^c Naphthalen-1-ol.

^d 2-[3-(Methylamino)-1-(thiophen-2-yl)propyl naphthalen-1-ol

^e (S)-N-Methyl-3-(naphthalen-1-yloxy)-3-(thiophen-3-yl)propan-1-amine

^f 1-Fluoronaphthalene.

LIMIT OF DULOXETINE RELATED COMPOUND A

Mobile phase: Hexane and isopropyl alcohol (83:17). To 1 L of this mixture add 2 mL of diethylamine.

System suitability solution: 0.1 mg/ml. each of USP Duloxetine Hydrochloride RS and USP Duloxetine Related Compound A RS in Mobile phase. Sonication may be used to aid in dissolution

Sensitivity solution: 0.1 µg/ml of USP Duloxetine Hydrochloride RS in Mobile phase

Sample solution: 0.1 mg/ml. of Duloxetine Hydrochloride in Mobife phase. Sonication may be used to aid in dissolution.

Chromatographic system

(See Chromatography (521), System Suitability)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm x 25-cm; 5-um packing L40

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: 2 times the retention time of duloxetine

System suitability

Samples: System suitability solution and Sensitivity solution

(Non-The relative retention times for duloxetine and duloxetine related compound A are 1.0 and 1.3, respectively

Suitability requirements

Resolution: NLT 3.5 between duloxetine and duloxetine related compound A, System suitability solution

Tailing factor: 0.8-1.5 each for duloxetine and duloxetine related compound A, System suitability solution

Relative standard deviation: NMT 5.0% for duloxetine, System suitability solution

Signal-to-noise ratio: NLT 3, Sensitivity solution

Analysis

Sample: Sample solution

Calculate the percentage of duloxetine related compound A in the portion of Duloxetine Hydrochloride taken:

Result = (r_U/r_S) x 100

r_U = peak response of duloxetine related compound A from the Sample solution

r_S = sum of the peak responses of duloxetine and duloxetine related compound A from the Sample solution

Acceptance criteria: NMT 0.5%

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Protect from light. Store at room temperature.