Tubocurarine Chloride
;)
Tubocuraranium,7¢,12¢-dihydroxy-6,6¢-dimethoxy-2,2¢,2¢-trimethyl-chloride,hydrochloride,pentahydrate.
(+)-Tubocurarine chloride hydrochloride pentahydrate [41354-45-4].
Anhydrous 681.66 [57-94-3].
»Tubocurarine Chloride contains not less than 95.0percent and not more than 105.0percent of C37H41ClN2O6·HCl,calculated on the anhydrous basis.
Packaging and storage—
Preserve in tight containers.
Clarity of alcohol solution—
Asolution of 100mg in 10mLof alcohol is clear.
Identification—
A:
Infrared Absorption á197Kñ.
B:
The chromatogram of the Assay preparationobtained as directed in the Assayexhibits a major peak,the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparation.
C:
Asolution (1in 100)responds to the tests for Chloride á191ñ.
Specific rotation á781Sñ:
between +210
and +224.
and +224.
Test solution:
10mg per mL,in water,allowed to stand for 3hours.
Water,Method Iá921ñ:
not more than 12.0%.
Residue on ignition á281ñ:
not more than 0.25%.
Related compounds—
In the chromatogram obtained from the Assay preparationin the Assay,the sum of the responses of any peaks detected,other than the peak due to tubocurarine,is not more than 5.0%of the total of all peak responses.
Chloride content—
Dissolve about 300mg,accurately weighed,in 5mLof water,warming slightly to effect solution.Add 5mLof glacial acetic acid and 50mLof methanol,and cool to room temperature.Add 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 9.9%and not more than 10.7%of Cl is found,calculated on the anhydrous basis.
Assay—
Mobile phase—
Mix 3volumes of acetonitrile and 2volumes of methanol,and allow the mixture to attain room temperature.To 270mLof this solution in a 1-liter graduated cylinder add 20.0mLof 25%tetramethylammonium hydroxide solution in methanol,and add water to make 1liter.Adjust with phosphoric acid to a pHof 4.0,filter,and degas.
Standard preparation—
Dissolve an accurately weighed quantity of USP Tubocurarine Chloride RSin Mobile phaseto obtain a solution having a known concentration of about 0.3mg per mL.
Assay preparation—
Transfer 30mg of Tubocurarine Chloride,accurately weighed,to a 100-mLvolumetric flask.Dissolve in Mobile phase,dilute with Mobile phaseto volume,and mix.
System suitability preparation—
Dissolve suitable quantities of tubocurarine chloride and phenol in Mobile phaseto obtain a solution containing about 0.30mg and 0.50mg per mL,respectively.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a 220-nm detector,and a 4-mm ×25-cm column that contains packing L1.The flow rate is about 1mLper minute.Chromatograph the System suitability preparation,and record the peak responses as directed for Procedure:the resolution,R,between the two major peaks is not less than 2.0,and the tailing factor,T,for tubocurarine chloride is not more than 2.0.The relative standard deviation for replicate injections of the Standard preparationis not more than 2.0%.The relative retention times are about 0.50and 1.0for tubocurarine chloride and phenol,respectively.
Procedure—
Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C37H41ClN2O6·HCl in the portion of Tubocurarine Chloride taken by the formula:
100C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Tubocurarine Chloride RSin the Standard preparation,and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Ravi Ravichandran,Ph.D.,Senior Scientist
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 2000
Pharmacopeial Forum:Volume No.29(6)Page 1996
Phone Number:1-301-816-8330