Succinylcholine Chloride
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C14H30Cl2N2O4(anhydrous) 361.30

Ethanaminium,2,2¢-[(1,4-dioxo-1,4-butanediyl)bis(oxy)]bis[N,N,N-trimethyl]-,dichloride.
Choline chloride succinate (2:1) [71-27-2].

Dihydrate 397.34 [6101-15-1].
»Succinylcholine Chloride usually contains approximately two molecules of water of hydration.It contains not less than 96.0percent and not more than 102.0percent of C14H30Cl2N2O4,calculated on the anhydrous basis.
Packaging and storage— Preserve in tight containers.Store at 25,excursions permitted between 15and 30.
Labeling— Label it in terms of its anhydrous equivalent.Where it is intended for use in preparing injectable or other sterile 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 á197Kñ.
B: The retention time of the major peak in the chromatogram of the Assay preparationcorrespond to that in the chromatogram of the Standard preparation,as obtained in the Assay.
C: Dissolve a portion in water to obtain a solution containing 1mg per mL.Applying 1-µLportions to a plate coated with a 0.25-mm layer of chromatographic silica gel (see Chromatography á621ñ),and using a solvent system consisting of a mixture of acetone and 1Nhydrochloric acid (1:1),proceed as directed under Thin-layer Chromatographic Identification Test á201ñ.Use the following procedure to locate the spots.Heat the plate at 105for 5minutes,cool,and spray with potassium bismuth iodide TS,then heat again at 105for 5minutes.
Water,Method Iá921ñ: not more than 10.0%.
Residue on ignition á281ñ: not more than 0.2%.
Limit of ammonium salts— To about 200mg add 5mLof sodium carbonate TS,and bring to a boil:no odor of ammonia is evolved.
Chromatographic purity—
TEST1—
Buffer solution— Prepare a solution in water containing 3.85g per Lof 1-pentanesulfonic acid,2.9g per Lof sodium chloride,and 1%(v/v)of 1Nsulfuric acid.
Mobile phase— Prepare a filtered and degassed mixture of acetonitrile and Buffer solution (5:95).
System suitability solution— Dissolve accurately weighed quantities of citric acid and succinic acid in Mobile phase;to obtain a solution containing about 0.5mg of each per mL.
Standard solution— Dissolve an accurately weighed quantity of USP Succinylmonocholine Chloride RSin Mobile phase;and dilute quantitatively,and stepwise if necessary,with Mobile phase to obtain a solution having a known concentration of about 0.05mg per mL.
Test solution— Transfer about 100mg of Succinylcholine Chloride,accurately weighed,to a 10-mLvolumetric flask;and dissolve in and dilute with Mobile phase to volume.
Chromatographic system (see Chromatography á621ñ)— The chromatograph is equipped with a 214-nm detector and a 4.6-mm ×25-cm column that contains 5-µm packing L1.The flow rate is about 1mLper minute.Samples are maintained at a temperature of about 4during the analysis.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.22for succinic acid,0.32for the doublet of peaks quantitated as a single component,0.49for succinylmonocholine chloride,and 1.0for succinylcholine chloride;the resolution,R,between citric acid and succinic acid is not less than 2.9;and the relative standard deviation for replicate injections is not more than 3.0%.
Procedure— Separately inject equal volumes (about 50µL)of the Standard solution and the Test solution into the chromatograph,record the chromatograms,and measure the peak responses.Begin integration after the edetate disodium peak (retention time is about 3.5minutes).Calculate the percentage of each impurity in the portion of Succinylcholine Chloride taken by the formula:
10C(ri/rS)F,
in which Cis the concentration,in mg per mL,of USP Succinylcholine Chloride RSin the Standard solution;riis the peak area for each impurity obtained from the Test solution;rSis the succinylmonocholine chloride peak area obtained from the Standard solution;and Fis the response factor (0.63for succinic acid):not more than 0.1%of succinic acid is found;not more than 0.4%of the doublet of peaks quantitated as a single component is found;not more than 0.4%of succinylmonocholine chloride is found;and not more than 0.2%of any other individual impurity is found.
TEST2(LIMIT OF CHOLINE)—
Solution A— Prepare a solution in water containing 5%(v/v)of acetonitrile and 5%(w/v)of 0.1M1-hexanesulfonic acid.
Solution B— Prepare a solution of acetonitrile and water (1:1).
Mobile phase— Use variable amounts of Solution Aand Solution Bas directed for Chromatographic system.Make adjustments if necessary (see System Suitability under Chromatography á621ñ).
System suitability solution— Dissolve an accurately weighed quantity of USP Choline Chloride RSand sodium chloride in water;and dilute quantitatively,and stepwise if necessary,with water to obtain a solution containing 0.05mg per mLand 0.5mg per mL,respectively.
Standard stock solution— Dissolve an accurately weighed quantity of USP Choline Chloride RSin water;and dilute quantitatively,and stepwise if necessary,with water to obtain a solution containing 0.5mg per mL.
Standard solution— Dilute 1mLof the Standard stock solution with water to 50mL.
Test solution— Transfer an accurately weighed quantity of Succinylcholine Chloride,about 50mg,to a 25-mLflask.Dissolve in and dilute with water to volume.
Chromatographic system (see Chromatography á621ñ)— The ion chromatograph is equipped with a cation self-regenerating suppressor,a conductivity detector at 30µSand a 4.6-mm ×25-cm column that contains 5-µm packing L1.The eluant flow is about 1mLper minute and the regenerant flow is about 10mLper minute at 50mAoutput.The chromatograph is programmed as follows.
Time
(minutes)		 Solution A
(%)		 Solution B
(%)
Elution
0–15 100 0 isocratic
15–16 100®0 0®100 linear gradient
16–25 0 100 isocratic
25–27 0®100 100®0 linear gradient
27–40 100 0 isocratic
Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the resolution,R,between the sodium and choline peaks is not less than 2.0;and the relative standard deviation for replicate injections is not more than 3.0%.
Procedure— Separately inject equal volumes (about 50µL)of the Standard solution and the Test solution into the chromatograph,record the chromatograms,and measure the peak responses.Calculate the percentage of choline in the portion of Succinylcholine Chloride taken by the formula:
37.5C(rC/rS),
in which Cis the concentration,in mg per mL,of USP Choline Chloride RSin the Standard solution;and rCand rSare the choline peak areas obtained from the Test solution and the Standard solution,respectively:not more than 0.3%of choline is found.Calculate the percentage of any other impurity present by the formula:
50C(ri/rS),
in which Cis the concentration,in mg per mL,of USP Choline Chloride RSin the Standard solution;riis the peak area of each impurity obtained from the Test solution;and rSis the choline peak area obtained from the Standard solution:not more than 1.5%of total impurities is found,the results for Test 1and Test 2being added.
Chloride content— Dissolve about 400mg,accurately weighed,in 5mLof water.Add 5mLof glacial acetic acid,50mLof methanol,and 1drop of eosin Y TS,and titrate with 0.1Nsilver nitrate VS.Each mLof 0.1Nsilver nitrate is equivalent to 3.545mg of Cl.Not less than 19.3%and not more than 19.8%of Cl,calculated on the anhydrous basis,is found.
Other requirements— Where the label states that Succinylcholine Chloride is sterile,it meets the requirements for Sterility Tests á71ñand for Bacterial endotoxinsunder Succinylcholine Chloride for Injection.Where the label states that Succinylcholine Chloride must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements for Bacterial endotoxinsunder Succinylcholine Chloride for Injection.
Assay— [NOTE—Since the Mobile phase employed in this procedure has a fairly high concentration of chloride ion and a low pH,it is advisable to rinse the entire system with water following the use of this Mobile phase.]
Mobile phase— Prepare a 1in 10solution of 1Naqueous tetramethylammonium chloride in methanol.Pass this solution through a 0.45-µm membrane filter,and adjust with hydrochloric acid to a pHof about 3.0.
Standard preparation— Transfer about 88mg of USP Succinylcholine Chloride RS,accurately weighed,to a 10-mLvolumetric flask,add 4.0mLof water,and dilute with Mobile phase to volume while mixing.Prepare the Standard preparation concurrently with the Assay preparation.
Assay preparation— Transfer about 88mg of Succinylcholine Chloride,accurately weighed,to a 10-mLvolumetric flask,add 4.0mLof water,and dilute with Mobile phase to volume while mixing.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 214-nm detector and a 4-mm ×25-cm column that contains packing L3.The flow rate is about 0.75mLper minute.Chromatograph five replicate injections of the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor is not greater than 2.5;and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure— Separately inject equal volumes (about 10µL)of the Standard preparation and the Assay preparation into the chromatograph by means of a suitable microsyringe or sampling valve,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C14H30Cl2N2O4in the Succinylcholine Chloride taken by the formula:
10C(rU/rS),
in which Cis the concentration,in mg per mL,of anhydrous succinylcholine chloride in the Standard preparation,as determined from the concentration of USP Succinylcholine Chloride RScorrected for moisture content by a titrimetric water determination;rUis the peak response obtained from the Assay preparation;and rSis the average peak response obtained from the Standard preparation.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 1807
Pharmacopeial Forum:Volume No.29(6)Page 1984
Phone Number:1-301-816-8379