Buspirone 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

Buspirone Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of buspirone hydrochloride (C₂₁H₃₁N₅O₂·HCl)

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

Sample: Grind 20 Tablets to a fine powder, add 50 mL of chloroform, stir for 3–5 min, and filter into a 250-mL evaporating flask. Evaporate the solution with the aid of a rotary evaporator to dryness at low heat. Use the residue.

Acceptance criteria: Meet the requirements

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

Procedure

Buffer A: 6.8 g/L of monobasic potassium phosphate and 0.93 g/L of sodium 1-hexanesulfonate monohydrate, adjusted with phosphoric acid to a pH of 3.4

Buffer B: 3.4 g/L of monobasic potassium phosphate and 3.52 g/L of sodium 1-hexanesulfonate monohydrate, adjusted with phosphoric acid to a pH of 2.2

Solution A: Acetonitrile and Buffer A (5:95)

Solution B: Acetonitrile and Buffer B (75:25)

Mobile phase: See Table 1.

Diluent: Solution A

Impurities stock solution: 0.25 mg/mL each of USP Buspirone Related Compound A RS, USP Buspirone Related Compound G RS, USP Buspirone Related Compound K RS, USP Buspirone Related Compound L RS, and USP Buspirone Related Compound N RS in acetonitrile

System suitability solution: 1.0 mg/mL of USP Buspirone Hydrochloride RS and 0.001 mg/mL each of USP Buspirone Related Compound A RS, USP Buspirone Related Compound G RS, USP Buspirone Related Compound K RS, USP Buspirone Related Compound L RS, and USP Buspirone Related Compound N RS in Diluent from the Impurities stock solution

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

Sample solution: Nominally 0.1 mg/mL of buspirone hydrochloride from NLT 20 finely powdered Tablets in Diluent, prepared as follows. Transfer a suitable amount of the powder to a suitable volumetric flask. Add 60% of the flask volume of Diluent, and sonicate for 30 min. Allow the solution to cool to room temperature, and then dilute with Diluent to volume. Centrifuge the solution and filter the supernatant. Further dilute the filtrate with Diluent as needed.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

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

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between the buspirone and buspirone related compound G peaks, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of buspirone hydrochloride (C₂₁H₃₁N₅O₂·HCl) in the portion of Tablets taken:

Result = (r₁/r₂) × (C₁/C₂) × 100

r₁ = peak response from the Sample solution

r₂ = peak response from the Standard solution

C₁ = concentration of USP Buspirone Hydrochloride RS in the Standard solution (mg/mL)

C₂ = nominal concentration of buspirone hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.01 N hydrochloric acid; 500 mL

Apparatus 2: 50 rpm with suitable sinker, if needed

Time: 30 min

Sample solution: Filter a portion of the solution under test, and dilute with Medium as needed.

Standard solution: USP Buspirone Hydrochloride RS in Medium having a concentration similar to that expected in the Sample solution

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum at about 235 or 237 nm

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of the labeled amount of buspirone hydrochloride (C₂₁H₃₁N₅O₂·HCl) dissolved:

Result = (A₁/A₂) × C × V × (1/L) × 100

A₁ = absorbance of the Sample solution

A₂ = absorbance of buspirone hydrochloride from the Standard solution

C = concentration of USP Buspirone Hydrochloride RS in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of buspirone hydrochloride (C₂₁H₃₁N₅O₂·HCl) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Buffer A, Buffer B, Solution A, Solution B, Mobile phase, Diluent, Impurities stock solution, and System suitability solution: Proceed as directed in the Assay.

Standard solution: 0.001 mg/mL each of USP Buspirone Hydrochloride RS, USP Buspirone Related Compound A RS, USP Buspirone Related Compound G RS, USP Buspirone Related Compound K RS, USP Buspirone Related Compound L RS, and USP Buspirone Related Compound N RS in Diluent

Sample solution: Nominally 1.0 mg/mL of buspirone hydrochloride from NLT 20 finely powdered Tablets in Diluent, prepared as follows. Transfer a suitable amount of the powder to a suitable volumetric flask. Add 60% of the flask volume of Diluent, and sonicate for 30 min. Allow the solution to cool to room temperature, and then dilute with Diluent to volume. Centrifuge the solution and filter the supernatant. Use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 and 240 nm

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

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution at 240 nm: NLT 2.0 between the buspirone and buspirone related compound G peaks, System suitability solution

Resolution at 210 nm: NLT 4.0 between the buspirone related compound L and buspirone related compound N peaks, System suitability solution

Relative standard deviation: NMT 2.0% for each peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

For impurities detected at UV 240 nm:

Calculate the percentage of buspirone related compound A in the portion of Tablets taken:

Result = (r₁/r₂) × (C₁/C₂) × 100

r₁ = peak response of buspirone related compound A from the Sample solution

r₂ = peak response of buspirone related compound A from the Standard solution

C₁ = concentration of USP Buspirone Related Compound A RS in the Standard solution (mg/mL)

C₂ = nominal concentration of buspirone hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of any individual unspecified degradation product in the portion of Tablets taken:

Result = (r₁/r₂) × (C₁/C₂) × 100

r₁ = peak response of any individual unspecified degradation product from the Sample solution

r₂ = peak response of buspirone from the Standard solution

C₁ = concentration of USP Buspirone Hydrochloride RS in the Standard solution (mg/mL)

C₂ = nominal concentration of buspirone hydrochloride in the Sample solution (mg/mL)

Acceptance criteria:

For impurities detected at UV 240 nm: See Table 2 (below). Disregard any peak below 0.05%.

a 2-(Piperazin-1-yl)pyrimidine.

b 8-(Pyrimidin-2-yl)-8-aza-5-azoniaspiro[4.5]decane.

c Process impurity included for identication only and not included in the calculation of total degradation products.

d 1,4-Bis[4-(pyrimidin-2-yl)piperazin-1-yl]butane.

e Bis{4-[1-(pyrimidine-2-yl)piperazine-4-yl]butane-1-yl} ether.

f 2-{1-[2-Oxo-2-({4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl}amino)ethyl]cyclopentyl}acetic acid.

g 4-[4-(Pyrimidin-2-yl)piperazin-1-yl]butyl 2-{1-[2-oxo-2-({4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl}amino)ethyl]cyclopentyl}acetate.

h 1,4-Di(pyrimidin-2-yl)piperazine.

i Bis{4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl} 2,2'-(cyclopentane-1,1-diyl)diacetate.

j 8-{4-[4-(5-Chloropyrimidin-2-yl)piperazin-1-yl]butyl}-8-azaspiro[4.5]decane-7,9-dione.

k 4-(7,9-Dioxo-8-azaspiro[4.5]decan-8-yl)butyl 2-{1-[2-oxo-2-({4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl}amino)ethyl]cyclopentyl}acetate.

For impurities detected at UV 210 nm:

Calculate the percentage of any individual unspecified degradation product in the portion of Tablets taken:

Result = (r₁/r₂) × (C₁/C₂) × 100

r₁ = peak response of any individual unspecified degradation product from the Sample solution

r₂ = peak response of buspirone from the Standard solution

C₁ = concentration of USP Buspirone Hydrochloride RS in the Standard solution (mg/mL)

C₂ = nominal concentration of buspirone hydrochloride in the Sample solution (mg/mL)

Acceptance criteria:

For impurities detected at UV 210 nm: See Table 3. Disregard any peak below 0.05%.

a 8-Azaspiro[4.5]decane-7,9-dione.

b Process impurity included for identication only and not included in the calculation of total degradation products.

c 8-(4-Chlorobutyl)-8-azaspiro[4.5]decane-7,9-dione.

d 8-(4-Bromobutyl)-8-azaspiro[4.5]decane-7,9-dione.

e 8,8'-(Butane-1,4-diyl)bis(8-azaspiro[4.5]decane-7,9-dione).

f Total impurities include impurities detected at UV 240 nm.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers at controlled room temperature.

USP Reference Standards 〈11〉

USP Buspirone Hydrochloride RS

USP Buspirone Related Compound A RS

2-(Piperazin-1-yl)pyrimidine. C₈H₁₂N₄ 164.21

USP Buspirone Related Compound G RS

1,4-Di(pyrimidin-2-yl)piperazine. C₁₂H₁₄N₆ 242.28

USP Buspirone Related Compound K RS

8-Azaspiro[4.5]decane-7,9-dione. C₈H₁₁NO₂ 167.21

USP Buspirone Related Compound L RS

8-(4-Chlorobutyl)-8-azaspiro[4.5]decane-7,9-dione. C₁₂H₁₉ClNO₂ 257.76

USP Buspirone Related Compound N RS

8,8'-(Butane-1,4-diyl)bis(8-azaspiro[4.5]decane-7,9-dione). C₂₂H₃₂N₂O₄ 388.50