Nefazodone Hydrochloride

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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C₂₅H₃₂ClN₅O₂  · HCl       506.47

3H-1,2,4-Triazol-3-one, 2-[3-[4-(3-chlorophenyl)-1-piperazinyl)]propyl]-5-ethyl-2,4-dihydro-4-(2-phenoxyethyl)-, monohydrochloride;

1-[3-[4-(m-Chlorophenyl)-1-piperazinyl]propyl]-3-ethyl-4-(2-phenoxyethyl)-Δ2-1,2,4-triazolin-5-one monohydrochloride

2-{3-[4-(3-Chlorophenyl)piperazin-1-yl]propyl}-5-ethyl-4-(2-phenoxyethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

CAS RN: 82752-99-6; UNII: 27X63J94GR.

1 DEFINITION

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Nefazodone Hydrochloride contains NLT 98.0% and NMT 102.0% of nefazodone hydrochloride _{(USP 1-May-2021)} (C₂₅H₃₂ClN₅O₂  · HCl). calculated on the dried basis.

2 IDENTIFICATION

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

B. IDENTIFICATION TESTS GENERAL (191), Chemical Identification Tests. Chloride

Sample solution: 10 mg/mL in methanol

Acceptance criteria: Meets the requirements

Add the following:

C. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay (USP 1-May-2021)

3 ASSAY

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PROCEDURE

Solution A: 0.77 g/L of ammonium acetate in water. Adjust with triethylamine to a pH of 7.10 ± 0.05, and degas.

Solution B: Acetonitrile ( degassed)

Mobile phase: See Table 1.

Table 1

Impurities stock solution: 0.1 mg/mL of USP Nefazodone Related Compound A RS and USP Nefazodone Related Compound B. RS in Diluent

System suitability stock solution: 0.1 mg/mL of USP Nefazodone Hydrochloride RS in Diluent

System suitability solution: 5 µg/mL each of USP Nefazodone Related Compound A RS and USP Nefazodone Related Compound B RS from the Impurities stock solution in the System suitability stock solution

Standard solution: 0.5 mg/mL of USP Nefazodone Hydrochloride RS in Diluent

Sample solution: 0.5 mg/mL of Nefazodone Hydrochloride in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 250 nm.

Column: 4.6-mm x 25-cm; 5-µm packing L1

Flow rate: 1.7 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 4.0 between nefazodone related compound A and nefazodone; NLT 1.5 between nefazodone and nefazodone related compound B, System suitability solution

Relative standard deviation: NMT 0.73% for nefazodone, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of nefazodone hydrochloride (C₂₅H₃₂ClN₅O₂  · HCl) in the portion of Nefazodone Hydrochloride taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of nefazodone from the Sample solution

r_s = peak response of nefazodone from the Standard solution

C_s = concentration of USP Nefazodone Hydrochloride RS in the Standard solution (mg/mL)

C_u = concentration of Nefazodone Hydrochloride in the Sample solution (mg/mL) _{(USP 1-May-2021)}

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

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ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, Impurities stock solution, and Chromatographic system: Proceed as directed in the Assay. _{(USP 1-May-2021)}

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

System suitability solution: 5 µg/mL each of USP Nefazodone Related Compound A RS and USP Nefazodone Related Compound B RS from.

the Impurities stock solution in the Standard stock solution

Standard solution: 0.001 mg/mL (USP 1-May-2021) each of USP Nefazodone Hydrochloride RS. _{(USP 1-May-2021)} USP Nefazodone Related Compound A RS, and USP Nefazodone Related Compound B RS from the Standard stock solution and the Impurities stock solution in Diluent

Sample solution: 1 mg/mL of Nefazodone Hydrochloride in Diluent A _{(USP 1-May-2021)}

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 4.0 between nefazodone related compound A and nefazodone; _{(USP 1-May-2021)} NLT 1.5 between nefazodone _{(USP 1-May-2021)} and nefazodone related compound B, System suitability solution Relative standard deviation: NMT 5.0% for nefazodone related compound A and nefazodone related compound B, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each nefazodone related compound in the portion of Nefazodone Hydrochloride taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak area of the corresponding nefazodone related compound from the Sample solution

r_s = peak area of the corresponding nefazodone related compound from the Standard solution

C_s = concentration of the corresponding _{(USP 1-May-2021)} USP Reference Standard in the Standard solution (mg/mL)

C_u = concentration of Nefazodone Hydrochloride in _{(USP 1-May-2021)} the Sample solution (mg/mL)

Calculate the percentage of any unspecied impurity in the portion of Nefazodone Hydrochloride taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak area of any unspecied impurity from the Sample solution

r_s = peak area of nefazodone from the Standard solution

C_s = concentration of USP Nefazodone Hydrochloride RS in the Standard solution (mg/mL)

C_u = concentration of Nefazodone Hydrochloride in the Sample solution (mg/mL) _{(USP 1-May-2021)}

Acceptance criteria: See Table 2.

Table 2 _{(USP 1-May-2021)}

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry under vacuum at 105° for 3 h.

Acceptance criteria: NMT 0.5%

Completeness of Solution 〈641〉

Sample solution: 25 mg/mL in methanol

Acceptance criteria: Meets the requirements

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store between 15° and 30°.

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USP Reference Standards 〈11〉

USP Nefazodone Hydrochloride RS

USP Nefazodone Related Compound A RS

1-(3-Chloropropyl)-4-(3- _{(USP 1-May-2021)} chlorophenyl)piperazine hydrochloride. _{(USP 1-May-2021)}

C₁₃H₁₈Cl₂N₂ · HCl             309.66 _{(USP 1-May-2021)}

USP Nefazodone Related Compound B RS

2-{3-(4-(4- _{(USP 1-May-2021)} Chlorophenyl)-1-piperazinyl)propyl}-5-ethyl-2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one hydrochloride. _{(USP 1-May-2021)}

C₂₅H₃₂ClN₅O₂  · HCl         506.47 _{(USP 1-May-2021)}