Risperidone Oral Solution
DEFINITION
Risperidone Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of risperidone (C23H27FN4O2). It may contain a suitable preservative.
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
5.0 g/L of ammonium acetate in water
Mobile phase:
Acetonitrile and Buffer (11:39)
Standard stock solution:
1 mg/mL of USP Risperidone RS, in methanol
Standard solution:
0.2 mg/mL of USP Risperidone RS prepared from the Standard stock solution as follows: Transfer 5.0 mL of the Standard stock solution to a 25-mL volumetric flask. Add 5.0 mL of water followed by 12.5 mL of Buffer, and allow to cool to room temperature. Dilute with methanol to volume.
Sample solution:
Nominal concentration of 0.2 mg/mL of risperidone prepared from Oral Solution as follows: Transfer an amount of Oral Solution, equivalent to 5 mg of risperidone to a 25-mL volumetric flask, add 12.5 mL of Buffer, fill with methanol almost to volume, and mix well. Allow to cool to room temperature, and dilute with methanol to volume.
System suitability solution:
0.25 mg/mL of USP Risperidone Related Compounds Mixture RS prepared as follows: Weigh USP Risperidone Related Compounds Mixture RS into a suitable volumetric flask. Dissolve first in 20% of the flask volume of methanol. Add 20% of the flask volume of water followed by 50% of the flask volume of Buffer, and allow to cool to room temperature. Dilute with methanol to volume.
Chromatographic system
Mode:
LC
Detector:
UV 275 nm
Column:
4.6-mm × 10-cm; 3-µm packing L1
Flow rate:
1.5 mL/min
Injection size:
10 µL
Run time:
2 times the retention time of risperidone
System suitability
Samples:
Standard solution and System suitability solution
Relative retention times:
See Impurity Table 1.
Suitability requirements
Resolution:
NLT 1.5 between bicyclorisperidone and Z-oxime, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C23H27FN4O2 in the portion of risperidone taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response for risperidone from the Sample solution |
| rS | = | = peak response for risperidone from the Standard solution |
| CS | = | = concentration of USP Risperidone RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of risperidone in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Deliverable Volume 
698
:
Meets the requirements
698:
Meets the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer, Mobile phase, Sample solution, Chromatographic system, and System suitability solution:
Proceed as directed in the Assay
Standard stock solution:
5 µg/mL of USP Risperidone RS, in methanol
Standard solution:
1 µg/mL of USP Risperidone RS from the Standard stock solution prepared as follows: Transfer 5.0 mL of the Standard stock solution to a 25-mL volumetric flask. Add 5.0 mL of water followed by 12.5 mL of Buffer, and allow to cool to room temperature. Dilute with methanol to volume.
System suitability
Samples:
System suitability solution and Standard solution
Relative retention times:
See Impurity Table 1.
Suitability requirements
Resolution:
NLT 1.5 between bicyclorisperidone and Z-oxime, System suitability solution
Relative standard deviation:
NMT 10%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of risperidone taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response for each individual impurity from the Sample solution |
| rS | = | = peak response for risperidone from the Standard solution |
| CS | = | = concentration of USP Risperidone RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of risperidone in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 1.0%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Risperidone cis N-oxidea | 0.33 | 0.97 | 0.50 |
| Bicyclorisperidoneb | 0.43 | 0.67 | 0.50 |
| Z-Oximec | 0.53 | — | — |
| Risperidone | 1.0 | — | — |
| Any unspecified degradation product | — | 1.0 | 0.20 |
|
a
cis-3-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one,N-oxide monohydrate.
b
3-(4-Fluoro-2-hydroxyphenyl)-1-[2-(6,7,8,9-tetrahydro-2-methyl-4-oxo-4H-pyrido-[1,2-a]pyrimidin-3-yl)ethyl]-1-aza-2-azoniabicyclo[ 2.2.2]oct-2-ene salt.
c
(Z)-3-[2-[4-(2,4-Difluorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.
[Note—Process impurity, not to be quantified in drug product: it is used to establish system suitability only. ] |
|||
SPECIFIC TESTS
• pH 791:
2.0–4.0
791:
2.0–4.0
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in light-resistant containers. Store at controlled room temperature. Do not freeze.
• USP Reference Standards 11
11
USP Risperidone RS 
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 410.48 CAS-106266-06-2
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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 410.48 CAS-106266-06-2
USP Risperidone Related Compounds Mixture RS
Contains a 98.9:0.5:0.30:0.3 (area %) mixture of four compounds:
98.9% of Risperidone.
0.5% of Risperidone cis-N-oxide: cis-3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one].
0.3% of Bicyclorisperidone: 3-(4-fluoro-2-hydroxyphenyl)-1-[2-(6,7,8,9-tetrahydro-2-methyl-4-oxo-4H-pyrido-[1,2-a]pyrimidin-3-yl)ethyl]-1-aza-2-azoniabicyclo[2.2.2]oct-2-ene iodide.
0.3% of Z-oxime: (Z)-3-[2-[4-(2,4-difluorophenyl) (hydroxyimino)methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.
Contains a 98.9:0.5:0.30:0.3 (area %) mixture of four compounds:
98.9% of Risperidone.
0.5% of Risperidone cis-N-oxide: cis-3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one].
0.3% of Bicyclorisperidone: 3-(4-fluoro-2-hydroxyphenyl)-1-[2-(6,7,8,9-tetrahydro-2-methyl-4-oxo-4H-pyrido-[1,2-a]pyrimidin-3-yl)ethyl]-1-aza-2-azoniabicyclo[2.2.2]oct-2-ene iodide.
0.3% of Z-oxime: (Z)-3-[2-[4-(2,4-difluorophenyl) (hydroxyimino)methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4572
Pharmacopeial Forum: Volume No. 35(4) Page 870