Pralidoxime Chloride for Injection

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

Pralidoxime Chloride for Injection contains NLT 90.0% and NMT 110.0% of the labeled amount of pralidoxime chloride (C₇H₉ClN₂O). 

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A, 197K, or 197M (CN 1-May-2020)

B. Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride: A solution (1 in 10) meets the requirements.

C. 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

Solution A: Prepare a solution containing 8 mM sodium octanesulfonate and 2 mM tetraethylammonium chloride as follows. Transfer 1.87 g of sodium octanesulfonate monohydrate and 330 mg of tetraethylammonium chloride to a 1-L volumetric flask, add water to dissolve the mixture, and dilute with water to volume. Adjust with 0.01 N hydrochloric acid to a pH of 4.3.

Mobile phase: Acetonitrile and Solution A (17:83)

Diluent: Acetonitrile and water (17:83)

Standard stock solution: 1.25 mg/mL of USP Pralidoxime Chloride RS in water. Use sonication to dissolve, if necessary. Standard solution: 0.125 mg/mL of USP Pralidoxime Chloride RS in Diluent from the Standard stock solution Sample stock solution: Nominally 1.25 mg/mL of pralidoxime chloride prepared as follows. Select a number of containers of Pralidoxime

Chloride for Injection, the combined contents of which are equivalent to about 10 g of pralidoxime chloride. Dissolve the contents of each container in water and combine all of the solutions in a 1000-mL volumetric flask. Rinse each container with water and add the rinsings to the volumetric flask. Dilute with water to volume and mix. Transfer 25.0 mL of the resulting solution to a 200-mL volumetric flask and dilute with water to volume.

Sample solution: Nominally 0.125 mg/mL of pralidoxime chloride in Diluent from the Sample stock solution. [Note—This solution is stable for up to 6 h when stored at room temperature protected from light.]

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm

Column: 4.6-mm × 15-cm; 3- or 3.5-µm packing L1

Flow rate: 0.5 mL/min

Injection volume: 10 µL

3.2 System suitability

Sample: Standard solution

[Note—USP Pralidoxime Chloride RS contains pralidoxime anti-isomer as a minor component. The relative retention times for pralidoxime anti-isomer and pralidoxime are 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between the pralidoxime anti-isomer and pralidoxime peaks

Tailing factor: NMT 1.5 for the pralidoxime chloride peak

Relative standard deviation: NMT 1.0% for the pralidoxime chloride peak

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pralidoxime chloride (C₇H₉ClN₂O) in the portion of Pralidoxime Chloride for Injection taken:

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

r_U = peak response of pralidoxime from the Sample solution

r_S = peak response of pralidoxime from the Standard solution

C_S = concentration of USP Pralidoxime Chloride RS in the Standard solution (µg/mL)

C_U = nominal concentration of pralidoxime chloride in the Sample solution (µg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 IMPURITIES

Organic Impurities

Solution A, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay. Standard stock solution: Use the Standard solution prepared as directed in the Assay.

Standard solution: 0.125 µg/mL of USP Pralidoxime Chloride RS in Diluent from the Standard stock solution

5.1 System suitability

Samples: Standard stock solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between the pralidoxime anti-isomer and pralidoxime peaks, Standard stock solution

Relative standard deviation: NMT 5.0% for the pralidoxime chloride peak, Standard solution

5.2 Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each impurity in the portion of Pralidoxime Chloride for Injection taken:

Result = (r_U /r ) × (C /C_U ) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of pralidoxime from the Standard solution

C_S = concentration of USP Pralidoxime Chloride RS in the Standard solution (µg/mL)

C_U = nominal concentration of pralidoxime chloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 1.

Table 1

^a(Z)-2-[(Hydroxyimino)methyl]-1-methylpyridin-1-ium chloride.

6 SPECIFIC TESTS

Constituted Solution: At the time of use, it meets the requirements for Injections and Implanted Drug Products 〈1〉, Product Quality Tests Common to Parenteral Dosage Forms, Specific Tests, Completeness and clarity of solutions

Bacterial Endotoxins Test 〈85〉: It contains NMT 0.10 USP Endotoxin Units/mg of pralidoxime chloride.

pH 〈791〉: 3.5–4.5, in a solution (1 in 20)

Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 2.0%

Sterility Tests 〈71〉: Meets the requirements

Other Requirements: It meets the requirements for Labeling 〈7〉, Labels and Labeling for Injectable Products.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging.

USP Reference Standards 〈11〉

USP Pralidoxime Chloride RS