Loxapine Succinate

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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1 DEFINITION

Loxapine Succinate contains NLT 98.0% _{(USP 1-Aug-2022)} and NMT 102.0% _{(USP 1-Aug-2022)} of loxapine succinate (C₁₈H₁₈ClN₃O · C₄H₆O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K or 197A (USP 1-Aug-2022)

Delete the following:

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Sample solution: 20 μg/mL in 0.01 N hydrochloric acid (USP 1-Aug-2022)

Add the following:

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1-Aug-2022)

3 ASSAY

Change to read:

Procedure

Buffer: 3.9 g/L of ammonium acetate in water. Adjust with 20% acetic acid or 6 N ammonium hydroxide to a pH of 7.3.

Solution A: Buffer

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and Buffer (70:30)

System suitability solution: 0.3 mg/mL of USP Loxapine Succinate RS and 0.45 μg/mL of USP Loxapine Related Compound A RS in Diluent

Standard solution: 0.3 mg/mL of USP Loxapine Succinate RS in Diluent

Sample solution: 0.3 mg/mL of Loxapine Succinate in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 10-cm; 2.7-μm packing L1

Column temperature: 35°

Flow rate: 1.4 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

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

Suitability requirements

Resolution: NLT 2.0 between loxapine and loxapine related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of loxapine succinate (C₁₈H₁₈ClN₃O · C₄H₆O₄) in the portion of Loxapine Succinate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of loxapine from the Sample solution

r_S = peak response of loxapine from the Standard solution

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

C_U = concentration of Loxapine Succinate in the Sample solution (mg/mL) (USP 1-Aug-2022)

Acceptance criteria: 98.0%–102.0% (USP 1-Aug-2022) on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

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Organic Impurities

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

Standard solution: 0.3 μg/mL each of USP Loxapine Succinate RS and USP Loxapine N-Oxide RS in Diluent (USP 1-Aug-2022)

System suitability

Samples: System suitability solution and (USP 1-Aug-2022) Standard solution [Note—See Table 2 for the relative retention times.] (USP 1-Aug-2022)

Suitability requirements

Resolution: NLT 2.0 between loxapine 

 (USP 1-Aug-2022) and loxapine related compound A, System suitability solution (USP 1-Aug-2022)

Relative standard deviation: NMT 5.0% for loxapine N-oxide and loxapine, (USP 1-Aug-2022) Standard solution

Signal-to-noise ratio: NLT 10 for loxapine N-oxide, Standard solution (USP 1-Aug-2022)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of loxapine N-oxide in the portion of Loxapine Succinate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of loxapine N-oxide from the Sample solution

r_S = peak response of loxapine N-oxide from the Standard solution

C_S = concentration of USP Loxapine N-Oxide RS in the Standard solution (mg/mL)

C_U = concentration of Loxapine Succinate in the Sample solution (mg/mL) (USP 1-Aug-2022)

Calculate the percentage of any other (USP 1-Aug-2022) individual impurity in the portion of Loxapine Succinate taken:

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

r_U = peak response of each other (USP 1-Aug-2022) impurity from the Sample solution

r_S = peak response of loxapine (USP 1-Aug-2022) from the Standard solution

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

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

F = relative response factor (see Table 2 (USP 1-Aug-2022) )

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

a 2-Chloro-11-(piperazin-1-yl)dibenzo[b,f][1,4]oxazepine.

b 2-Chlorodibenzo[b,f]-1,4-oxazepin-11-one.

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

Change to read:

 USP Reference Standards 〈11〉

 (USP 1-Aug-2022)

USP Loxapine Succinate RS

 USP Loxapine N-Oxide RS

4-(2-Chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazine 1-oxide.

C₁₈H₁₈ClN₃O₂ 343.81 (USP 1-Aug-2022)

USP Loxapine Related Compound A RS

3-Chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine.

C₁₈H₁₈ClN₃O 327.81