Pralidoxime Chloride
;)
Pyridinium,2-(hydroxyimino)methyl-1-methyl-,chloride.
2-Formyl-1-methylpyridinium chloride oxime [51-15-0].
»Pralidoxime Chloride contains not less than 97.0percent and not more than 102.0percent of C7H9ClN2O,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Labeling—
Where it is intended for use in preparing injectable dosage forms,the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
Identification—
A:
Infrared Absorption á197Mñ.
B:
Asolution (1in 10)responds to the tests for Chloride á191ñ.
C:
The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
Loss on drying á731ñ—
Dry it at 105
for 3hours:it loses not more than 2.0%of its weight.
for 3hours:it loses not more than 2.0%of its weight.
Residue on ignition á281ñ:
not more than 0.5%.
Heavy metals,Method Iá231ñ:
0.002%.
Chloride content—
Dissolve about 300mg,accurately weighed,in 150mLof water,add 20mLof glacial acetic acid and 10drops of (p-tert-octylphenoxy)nonaethoxyethanol,and titrate with 0.1Nsilver nitrate VS,determining the endpoint potentiometrically.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nsilver nitrate is equivalent to 3.545mg of Cl.Not less than 20.2%and not more than 20.8%,calculated on the dried basis,is found.
Other requirements—
Where the label states that Pralidoxime Chloride is sterile,it meets the requirements for Sterility Tests á71ñand for Bacterial endotoxinsunder Pralidoxime Chloride for Injection.Where the label states that Pralidoxime Chloride must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements for Bacterial endotoxinsunder Pralidoxime Chloride for Injection.
Assay—
Dilute phosphoric acid solution—
Transfer 10mLof phosphoric acid to a 100-mLvolumetric flask containing 50mLof water,and mix.Dilute with water to volume,and mix.
Tetraethylammonium chloride solution—
Transfer about 170mg of tetraethylammonium chloride to a 1-liter volumetric flask,add 3.4mLof Dilute phosphoric acid solution,and add water to dissolve the mixture.Dilute with water to volume,and mix.
Mobile phase—
Prepare a filtered and degassed mixture of acetonitrile and Tetraethylammonium chloride solution(52:48).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation—
Dissolve a suitable quantity of USP Pralidoxime Chloride RS,accurately weighed,in water to obtain a Standard solutionhaving a known concentration of about 1.25mg per mL.(Reserve a portion of the Standard solutionfor the System suitability preparation.)Pipet 2.0mLof this solution into a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Assay preparation—
Transfer about 62.5mg of Pralidoxime Chloride,accurately weighed,to a 50-mLvolumetric flask,dissolve in water,dilute with water to volume,mix,and filter.Pipet 2.0mLof this solution into a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
System suitability preparation—
Prepare a solution of pyridine-2-aldoxime in water having a concentration of 0.65mg per mL.Transfer 2.0mLof this solution to a 100-mLvolumetric flask,add 2.0mLof the Standard solution,dilute with Mobile phaseto volume,and mix.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a 270-nm detector and a 3-to 5-mm ×25-cm column containing 5-µm packing L1.The flow rate is about 1.2mLper minute.Chromatograph the Standard preparationand the System suitability preparationby injecting about 15µLof these preparations,and record the peak responses as directed for Procedure:the resolution,R,between the pyridine-2-aldoxime and pralidoxime chloride peaks is not less than 4.0;the column efficiency determined from the analyte peak is not less than 4000theoretical plates;the tailing factor for the analyte peak is not more than 2.5;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 15µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 0.6for pyridine-2-aldoxime and 1.0for pralidoxime chloride.Calculate the quantity,in mg,of C7H9ClN2Oin the portion of Pralidoxime Chloride taken by the formula:
2.5C(rU/rS),
in which Cis the concentration,in µg per mL,of USP Pralidoxime Chloride RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28–NF23Page 1602
Pharmacopeial Forum:Volume No.29(5)Page 1564
Phone Number:1-301-816-8251