Related compounds
Buffer solution, Solution A, Solution B, Mobile phase, Diluent, System suitability solution, and Chromatographic system
Prepare as directed in the Assay.
Standard solution
Use the Standard preparation, prepared as directed in the Assay.
Test solution
Use the Assay preparation.
Procedure
Inject equal volumes (about 10 µL) of the
Standard solution and the
Test solution into the chromatograph, and record the chromatogram. Identify the impurities using the relative retention times given in
Table 1, and measure the peak responses. Calculate the percentage of each risperidone related compound in the portion of Risperidone taken by the formula:
100(CS /CU)(rU / rS)(1/F)
in which
CS and
CU are the concentrations, in mg per mL, of risperidone in the
Standard solution and the
Test solution respectively;
rU is the peak area of each impurity obtained from the
Test solution; rS is the peak area of risperidone obtained from the
Standard solution; and
F is the relative response factor for each impurity relative to risperidone. In addition to not exceeding the limits in
Table 1, not more than 0.10% of any unknown impurity (use
F value of 1.0) is found and not more than 0.30% of the total impurities is found. Disregard the impurity peaks that are less than 0.05%.
Table 1
Related Compound |
Relative Retention Time (RRT) |
Relative Response Factor (F) |
Limit (%) |
E-oxime1 |
0.60 |
1.0 |
NMT 0.20 |
Z-oxime2 |
0.67 |
0.63 |
NMT 0.20 |
9-hydroxyrisperidone3 |
0.76 |
0.92 |
NMT 0.20 |
5-fluororisperidone4 |
0.94 |
1.0 |
NMT 0.20 |
Risperidone |
1.0 |
1.0 |
|
6-methylrisperidone5 |
1.2 |
0.95 |
NMT 0.20 |
1
3-[2-[4-[(E)-(2,4-Difluorophenyl)(hydroxyimino)methyl]piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one
|
2
3-[2-[4-[(Z)-(2,4-Difluorophenyl)(hydroxyimino)methyl]piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one
|
3
(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
|
4
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
|
5
(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
|
Assay
Buffer solution
Dissolve 15.4 g of ammonium acetate in 1 L of water. Adjust with 10% acetic acid to a pH of 6.5, and mix.
Solution A
Mix 100 mL of Buffer solution with 150 mL of methanol in a 1000-mL volumetric flask, and dilute with water to volume.
Solution B
Mix 100 mL of Buffer solution with 850 mL of methanol in a 1000-mL volumetric flask, and dilute with water to volume.
Mobile phase
Use variable mixtures of
Solution A and
Solution B as directed for
Chromatographic system. Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Diluent
Mix 100 mL of Buffer solution with 900 mL of water and 1000 mL of methanol.
Standard preparation
Dissolve an accurately weighed quantity of
USP Risperidone RS in
Diluent, and dilute quantitatively, and stepwise if necessary, with
Diluent to obtain a solution having a known concentration of about 1.0 mg per mL.
Assay preparation
Dissolve an accurately weighed quantity of Risperidone in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a concentration of about 1.0 mg per mL.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 275-nm detector and a 4.6-mm × 10-cm column that contains 3-µm packing L1. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 35
. The chromatograph is programmed as follows.
Time (minutes) |
Solution A
(%) |
Solution B
(%) |
Elution |
01 |
70 |
30 |
isocratic |
120 |
70®5 |
30®95 |
linear gradient |
2025 |
5 |
95 |
isocratic |
2527 |
5®70 |
95®30 |
linear gradient |
2735 |
70 |
30 |
re-equilbration |
Inject the
System suitability solution. Record the peak responses as directed for
Procedure, and identify the peaks due to
Z-oxime, 9-hydroxyrisperidone, 6-methylrisperidone, and risperidone using the relative retention times (RRT) from
Table 1; the resolution,
R, between
Z-oxime and 9-hydroxyrisperidone is not less than 2.8; the tailing factor for risperidone is not more than 1.5; and the relative standard deviation for replicate injections is not more than 2.0% for the risperidone peak.
Procedure
Separately inject equal volumes (about 10 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, and measure the responses for the risperidone peak. Calculate the quantity, in percent of C
23H
27FN
4O
2, in the portion of Risperidone taken by the formula:
100(CS /CU)(rU / rS)
in which
CS and
CU are the concentrations, in mg per mL, of risperidone in the
Standard preparation and the
Assay preparation, respectively; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.