Trazodone Hydrochloride Tablets

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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1 DEFINITION

Trazodone Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of trazodone hydrochloride (C₁₉H₂₂CIN₅O · HCI).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. 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

Change to read:

PROCEDURE

Buffer: 1.15 g/L of monobasic ammonium phosphate, adjusted with sodium hydroxide to a pH of 6.0

Mobile phase: Methanol and Buffer (75:25)

Standard solution: 0.1 mg/mL of USP Trazodone Hydrochloride RS in 0.01 N hydrochloric acid TS

Sample solution: Nominally 0.1 mg/mL of trazodone hydrochloride from finely powdered Tablets (NLT 20). Transfer a suitable quantity of the powder to a suitable volumetric flask. Dissolve in 0.01 N hydrochloric acid TS and dilute with 0.01 N hydrochloric acid TS to volume. Sonicate for about 30 min, and pass through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 246 nm. For Identification A, use a diode array detector in the range of 200-400 nm.

Column: 5-mm x 10-cm; 4-µm packing L1.

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: NLT 4.5 times the retention time of trazodone

System suitability

Sample: Standard solution

Suitability requirements

^▲Tailing factor: NMT 2.5_{▲(USP 1-May-2023)}

Relative standard deviation: NMT ^▲1.0%_{▲(USP 1-May-2023)}

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of trazodone hydrochloride (C₁₉H₂₂CIN₅O · HCI) in the portion of Tablets taken:

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

r_U = peak response of trazodone from the Sample solution

r_S = peak response of trazodone from the Standard solution

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

C_U = nominal concentration of trazodone hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1

Medium: 0.01 N hydrochloric acid TS: 900 mL

Apparatus 2: 50 rpm.

Time: 60 min

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

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of trazodone hydrochloride (C₁₉H₂₂CIN₅O · HCI) dissolved:

                          Result = (r_U/r_S) × C_S x V x (1/L) × 100

r_U = peak response of trazodone from the Sample solution

r_S = peak response of trazodone from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of trazodone hydrochloride (C₁₉H₂₂CIN₅O · HCI)

4.1.2 Test 2: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2

Medium: 0.01 N hydrochloric acid TS: ^▲500_{▲(USP 1-May-2023)} mL

Apparatus 2: ^▲75_{▲(USP 1-May-2023)} rpm

Time: ^▲15_{▲(USP 1-May-2023)}min

Buffer: To each liter of water add 5 mL of triethylamine, and adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (25:75)

Standard solution: ^▲(L/500)_{▲(USP 1-May-2023)} mg/mL of USP Trazodone Hydrochloride RS in Medium, where L is the label claim, in mg/Tablet _{▲(USP 1-May-2023)} Sonicate if necessary.

Sample solution: Pass the solution through a suitable filter of 0.45-µm pore size. Discard the first 5 mL of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 246 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 45°

Flow rate: 1.5 mL/min

Injection volume: ^▲5_{▲(USP 1-May-2023)} µL

Run time: NLT 1.6 times the retention time of trazodone

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of trazodone hydrochloride (C₁₉H₂₂CIN₅O · HCI) dissolved:

                          Result = (r_U/r_S) × C_S x V x (1/L) x 100

r_U = peak response of trazodone from the Sample solution

r_S = peak response of trazodone from the Standard solution 

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

V = volume of Medium, ^▲500_{▲(USP 1-May-2023)} mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of trazodone hydrochloride (C₁₉H₂₂CIN₅O · HCI) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Solution A: 6.75 g/L of monobasic potassium phosphate. Add 1.0 mL of triethylamine for each liter of the solution, and mix.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Methanol, water, and hydrochloric acid (650:350:3)

System suitability solution: 0.7 µg/mL of USP Trazodone Hydrochloride RS and 1.5 µg/mL of USP Trazodone Related Compound C RS in Diluent

Standard solution: 0.7 µg/mL of USP Trazodone Hydrochloride RS in Diluent

Sample solution: Nominally 500 µg/mL of trazodone ^▲hydrochloride _{▲(USP 1-May-2023)} from finely powdered Tablets (NLT 20) prepared as follows. Transfer a portion of powdered Tablets (^▲equivalent to _{▲(USP 1-May-2023)} NLT 50 mg ^▲of trazodone hydrochloride _{▲(USP 1-May-2023)}) to a suitable volumetric flask. Add about 80% of the flask volume of Diluent, and sonicate for 10 min. Dilute with Diluent to volume. Pass a portion of the solution through a suitable membrane filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.0-mm x 15-cm; 3-µm packing L1

Flow rate: 0.7 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 2.5 between trazodone related compound C and trazodone, ^▲_{▲(USP 1-May-2023)} System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

^▲Signal-to-noise ratio: NLT 10, Standard solution_{▲(USP 1-May-2023)}

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ^▲any _{▲(USP 1-May-2023)} degradation product in the portion of Tablets taken:

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

r_U = peak response of ^▲any_{▲(USP 1-May-2023)} degradation product from the Sample solution

r_S = peak response of trazodone from the Standard solution

C_S = concentration of USP Trazodone Hydrochloride RS in the Standard solution (µg/mL)

C_U = nominal concentration of trazodone ^▲hydrochloride_{▲(USP 1-May-2023)} in the Sample solution (µg/mL)

Acceptance criteria: See Table 2. ^▲The reporting threshold is 0.1%_{▲(USP 1-May-2023)}

Table 2

^a Process impurity included for identification only. Process impurities are controlled in the drug substance, and are not to be reported or included in the ^▲total degradation products _{▲(USP 1-May-2023)} for the drug product.

^b [1,2,4] Triazolo[4,3-a]pyridin-3(2H)-one.

^c 1-(3-Chlorophenyl)piperazine.

^d 3-[4-(3-Chlorophenyl)piperazin-1-yl]propan-1-ol.

^e 1-(3-[4-(3-Chlorophenyl)piperazin-1-yl]propyl)-[1,2,4]triazolo[4,3-a]pyridin-1-ium-3-olate.

^f 2,2'-([Ethane-1,1-diylbis(3-chloro-4,1-phenylene) bis(piperazine-4,1-diyl)]bis (propane-3,1-diyl)}bis([1,2,4]triazolo[4,3-a]pyridin-3(2H)-one).

^g 1-(3-Chlorophenyl)-4-(3-chloropropyl)piperazine.

^h 1,3-Bis(4-(3-chlorophenyl)piperazin-1-yl)propane.

ⁱ 1,4-Bis(3-chlorophenyl)piperazine.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at controlled room temperature.

LABELING: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

Change to read:

USP REFERENCE STANDARDS (11)

USP Trazodone Hydrochloride RS

USP Trazodone Related Compound C. RS

2-(3-[4-(4-Chlorophenyl)piperazin-1-yl)propyl)-[1,2,4]triazolo [4,3-a]pyridin-3(2H)-one hydrochloride.

C₁₉H₂₂CIN₅O · HCl                ^▲408.33_{▲(USP 1-May-2023)}