Risperidone

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

C₂₃H₂₇FN₄O₂ 410.48 

4H-Pyrido[1,2-a]pyrimidin-4-one, 3-[2-[4-(6-uoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-; 3-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidino]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one CAS RN®: 106266-06-2. 

1 DEFINITION 

Risperidone contains NLT 98.0% and NMT 102.0% of risperidone (C₂₃H₂₇FN₄O₂), 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 Standard solution, as obtained in the Assay. 

3 ASSAY 

Procedure 

Buffer: 5 g/L of ammonium acetate. Adjust with glacial acetic acid to a pH of 6.0, and pass the solution through a suitable filter. Solution A: Acetonitrile and tetrahydrofuran (80:20) 

Mobile phase: Buffer and Solution A (80:20) 

Standard stock solution: 1 mg/mL of USP Risperidone RS in solution prepared as follows. Dissolve a suitable amount of USP Risperidone RS in 20% of the nal volume with methanol. Dilute with Mobile phase to nal volume. Sonication may be used to aid in dissolution. Standard solution: 0.2 mg/mL of USP Risperidone RS in Mobile phase from Standard stock solution 

System suitability solution: 20 µg/mL of USP Risperidone Related Compound G RS in Standard solution 

Sample stock solution: 1 mg/mL of Risperidone in solution prepared as follows. Dissolve a suitable amount of Risperidone in 20% of the nal volume with methanol. Dilute with Mobile phase to nal volume. Sonication may be used to aid in dissolution. Sample solution: 0.2 mg/mL of Risperidone in Mobile phase from Sample stock solution 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 275 nm 

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

Column temperature: 50° 

Flow rate: 1.5 mL/min 

Injection volume: 10 µL 

Run time: 2 times the retention time of risperidone 

System suitability 

Samples: Standard solution and System suitability solution 

[Note—The relative retention times for risperidone and risperidone related compound G are 1.0 and 1.1, respectively.] Suitability requirements 

Resolution: NLT 1.5 between risperidone and risperidone related compound G, System suitability solution 

Tailing factor: NMT 2.0 for risperidone, Standard solution 

Relative standard deviation: NMT 1.0% for risperidone, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of risperidone (C₂₃H₂₇FN₄O₂) in the portion of Risperidone taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of risedronate  from the Sample solution 

r_S = peak response of risedronate  from the Standard solution 

C_S = concentration of USP Risperidone Sodium RS in the Standard solution (mg/mL)  

C_U = concentration of Risperidone Sodium in the Sample solution (mg/mL) 

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

4 IMPURITIES 

Residue on Ignition 〈281〉 

Sample: 2.0 g of Risperidone 

Acceptance criteria: NMT 0.1% 

Organic Impurities 

Solution A: 5 g/L of ammonium acetate. Adjust with glacial acetic acid to a pH of 6.0, and pass the solution through a suitable filter. 

Solution B: Acetonitrile and methanol (40:60) 

Mobile phase: See Table 1. 

Table 1 

System suitability solution: 20 µg/mL of USP Risperidone Related Compound G RS and 10 mg/mL of USP Risperidone RS in methanol. Sonication may be used to aid in dissolution. 

Standard solution: 20 µg/mL of USP Risperidone RS in methanol. Sonication may be used to aid in dissolution. Sample solution: 10 mg/mL of Risperidone in methanol. Sonication may be used to aid in dissolution. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 260 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L7 

Column temperature: 50° 

Flow rate: 2 mL/min 

Injection volume: 10 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—Identify the peaks using Table 2.] 

Suitability requirements 

Resolution: NLT 1.5 between risperidone and risperidone related compound G, System suitability solution Tailing factor: NMT 2.0 for risperidone, Standard solution 

Relative standard deviation: NMT 5.0% for risperidone, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each impurity in the portion of Risperidone taken: 

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

r_U = peak area of each impurity from the Sample solution

r_S = peak area of each impurityfrom the Diluted standard solution  

C_S = concentration of USP Risperidone RS in the Diluted standard solution (mg/mL)  

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

F = relative response factor for each impurity (see Table 2) 

Acceptance criteria: See Table 2. 

[Note—Disregard the impurity peaks less than 0.05%.] 

Table 2 

a 3-(2-[4-[(E)-(2,4-Diuorophenyl)(hydroxyimino)methyl]piperidin-1-yl]ethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one. b 3-[2-[4-[(Z)-(2,4-Diuorophenyl)(hydroxyimino)methyl]piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one. 

c(9RS)-3-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]ethyl]-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one. d 3-{2-[4-(Benzisoxazol-3-yl)piperidin-1-yl]ethyl}-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one. 

e This impurity may not be relevant to all manufacturing processes. 

f 3-[2-[4-(2,4-Diuorobenzoyl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one. 

g 3-[2-[4-(5-Fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (also known as 5- uororisperidone). 

h(6RS)-3-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]ethyl]-2,6-dimethyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one. 

5 SPECIFIC TESTS 

Loss on Drying 〈731〉 

Analysis: Dry under vacuum at 80° for 4 h. 

Acceptance criteria: NMT 0.5% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers. Store at room temperature. 

USP Reference Standards 〈11〉 

USP Risperidone RS 

USP Risperidone Related Compound G RS 

3-[2-[4-(4-Fluoro-2-hydroxybenzoyl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-α]pyrimidin-4-one hydrochloride. C₂₃H₂₈FN3O3· HCl 448.94