Paliperidone

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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C₂₃H₂₇FN₄O₃            426.48

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-9-hydroxy-2-methyl-; (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 CAS RN®: 144598-75-4; UNII: 838F01T721.

1 DEFINITION

Paliperidone contains NLT 98.0% and NMT 102.0% of paliperidone (C₂₃H₂₇FN₄O₃).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020) Do not dry the sample.

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

Protect the System suitability solution, Standard solution, and Sample solution from light.

Buffer: 28 mM Tetrabutylammonium hydrogen sulfate

Mobile phase: See Table 1.

Solution A: Methanol and Buffer (10:90)

Solution B: Methanol

Table 1

Diluent: Dissolve 0.71 g of dibasic sodium phosphate and 0.62 g of monobasic sodium phosphate in 1 L of water. System suitability solution: 0.5 mg/mL of USP Paliperidone Resolution Mixture RS prepared as follows. Dissolve first in methanol using 50% of the nal ask volume, and dilute with Diluent.

Standard solution: 0.5 mg/mL of USP Paliperidone RS prepared as follows. Dissolve first in methanol using 50% of the nal flask volume, and dilute with Diluent.

Sample solution: 0.5 mg/mL of Paliperidone prepared as follows. Dissolve first in methanol using 50% of the nal flask volume, and dilute with Diluent.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 275 nm

Column: 4.6-mm × 10-cm; 3-µm packing L1

Column temperature: 40°

Flow rate: 0.9 mL/min

Injection volume: 10 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between paliperidone related compound B and paliperidone; NLT 2.0 between paliperidone and paliperidone hydroxybenzoyl analog, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of paliperidone (C₂₃H₂₇FN₄O₃) in the portion of Paliperidone 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 Paliperidone RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%–102.0%

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Protect the System suitability solution, Standard solution, and Sample solution from light.

Diluent, Mobile phase, System suitability solution, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.5 µg/mL of USP Paliperidone RS in Diluent from Standard solution

4.1 System suitability

Samples: System suitability solution and Sensitivity solution

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between paliperidone related compound B and paliperidone; NLT 2.0 between paliperidone and paliperidone hydroxybenzoyl analog, System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Relative standard deviation: NMT 5.0%, Sensitivity solution

4.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Paliperidone taken:

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

r_U = peak response for each impurity from the Sample solution

r_S = peak response of paliperidone from the Standard solution

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

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

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

Acceptance criteria: See Table 2. Disregard any peak with area less than 0.05%.

Table 2

a 3-(2-Chloroethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one.

b 6-Fluoro-3-(piperidin-4-yl)benzoisoxazole.

c 3-{2-[4-(4-Fluoro-2-hydroxybenzoyl)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-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl]ethyl}-2-methyl-7,8-dihydro-4H-pyrido[1,2-a]pyrimidine-4,9(6H)-dione.

5 SPECIFIC TESTS

Water Determination, Method Ia 〈921〉: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP Paliperidone RS

USP Paliperidone Resolution Mixture RS

This contains paliperidone as the major component; it also contains paliperidone related compound B, paliperidone related compound C, paliperidone hydroxybenzoyl analog, and paliperidone ketone as minor components.