Buspirone 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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C₂₁H₃₁N₂O5 . HCI  421.96

8-Azaspiro [4,5]decane-7,9-dione, 8-[4-[4-(2-pyrimidinyl)-1-piperazinyl] butyl]-, monohydrochloride;

N-[4-[4-(2-Pyrimidinyl)-1-piperazinyl]butyl]-1,1-cyclopentanediacetamide monohydrochloride CAS RN^®: 33386-08-2; UNII: 207LT9J90C.

1 DEFINITION

Buspirone Hydrochloride contains NLT 97.5% and NMT 102.5% of buspirone hydrochloride (C₂₁H₃₁N₂O5 . HCI), calculated on the as-is basis.

2 IDENTIFICATION

Change to read:

A. ASPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K ( CN 1-MAY-2020)

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

C. IDENTIFICATION TESTS-GENERAL, Chloride (191).

Sample solution: 10 mg/mL in water

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 PROCEDURE

Buffer A: 6.8 g/L of monobasic potassium phosphate and 0.93 g/L of sodium 1-hexanesulfonate monohydrate. Adjust 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. Adjust 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.

Table 2

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 Impurities stock solution

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

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

Chromatographic system

(See Chromatography (621). System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm x 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 buspirone and buspirone related compound G peaks, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 0.92%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of buspirone hydrochloride (C₂₁H₃₁N₂O5 . HCI) in the portion of Buspirone Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 97.5%-102.5% on the as-is basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.5%

4.2 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: 1.0 mg/mL of Buspirone Hydrochloride in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 and 240 nm

Column: 4.6-mm x 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

[NOTE-See Table 2 and Table 3 for relative retention times.]

Suitability requirements

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

Resolution at 210 nm: NLT 4.0 between 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 or buspirone related compound G in the portion of Buspirone Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of buspirone related compound A or buspirone related compound G from the Sample solution

r_S = peak response of buspirone related compound A or buspirone related compound G from the Standard solution

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

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

Calculate the percentage of specified impurities and any other individual impurity in the portion of Buspirone Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of specified impurities and any other individual impurity from the Sample solution

r_S = peak response of buspirone from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria

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

Table 2

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

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

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

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

^e 2-(1-[2-0xo-2-({4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl)amino) ethyl]cyclopentyl)acetic acid.

^f 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.

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

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

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

^j 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 buspirone related compound K, buspirone related compound L, or buspirone related compound N in the portion of Buspirone Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r = peak response of buspirone related compound K, buspirone related compound L, or buspirone related compound N from the Sample solution

r = peak response of buspirone related compound K, buspirone related compound L, or buspirone related compound N from the Standard solution

C= concentration of USP Buspirone Related Compound K RS. USP Buspirone Related Compound L RS, or USP Buspirone Related Compound N RS in the Standard solution (mg/mL)

C= concentration of Buspirone Hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of buspirone bromobutyl analog and any other individual impurity in the portion of Buspirone Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of buspirone bromobutyl analog and any other individual impurity from the Sample solution

r_S = peak response of buspirone from the Standard solution s

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

C_U = 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%.

Table 3

^a 8-Azaspiro [4,5] decane-7,9-dione.

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

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

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

5 SPECIFIC TESTS

WATER DETERMINATION, Method (921): NMT 0.5%

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.

C₉H₁₃NO₂  167.21

USP Buspirone Related Compound L RS

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

C₁₃H₂₀CINO₂  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