Halothane
;)
Ethane,2-bromo-2-chloro-1,1,1-trifluoro-,(±)-.
(±)-2-Bromo-2-chloro-1,1,1-trifluoroethane [151-67-7].
»Halothane contains not less than 0.008percent and not more than 0.012percent of thymol,by weight,as a stabilizer.
Packaging and storage—
Preserve in tight,light-resistant containers,preferably of Type NPglass,and avoid exposure to excessive heat.Dispense it only in the original container.
Identification,Infrared Absorption á197Sñ.
Solution:
1in 25.
Medium:
carbon disulfide.
Specific gravity á841ñ:
between 1.872and 1.877at 20
.
.
Distilling range,Method IIá721ñ—
Not less than 95%distills within a 1range between 49and 51,and not less than 100%distills between 49and 51,a correction factor of 0.040per mm being applied as necessary.
range between 49and 51,and not less than 100%distills between 49and 51,a correction factor of 0.040per mm being applied as necessary.
Refractive index á831ñ:
between 1.369and 1.371at 20.
.
Acidity or alkalinity—
Shake 20mLwith 20mLof carbon dioxide-free water for 3minutes,and allow the layers to separate:the aqueous layer requires not more than 0.1mLof 0.010Nsodium hydroxide or not more than 0.6mLof 0.010Nhydrochloric acid for neutralization,bromocresol purple TSbeing used as the indicator.
Water,Method Iá921ñ:
not more than 0.03%.
Limit of nonvolatile residue—
Evaporate 50mLin a tared dish on a steam bath to dryness,and dry the residue at 105for 2hours:the weight of the residue does not exceed 1mg.
for 2hours:the weight of the residue does not exceed 1mg.
Chloride and bromide—
Shake 25mLwith 25mLof water for 5minutes,and allow the liquids to separate completely.Draw off the water layer,and to 10mLadd 1drop of nitric acid and 5drops of silver nitrate TS:no opalescence is produced.
Thymol content—
Standard thymol solution—
Prepare a standard solution of thymol in 0.25Nsodium hydroxide containing 0.1mg of thymol per mL.
Buffer solution—
Use pH8.0alkaline borate buffer (see under Solutionsin the section Reagents,Indicators,and Solutions).
Chlorimide solution—
Dissolve 100mg of 2,6-dibromoquinonechlorimide in 25mLof dehydrated alcohol.Prepare a fresh solution for each assay.
Standard thymol curve—
Pipet into three 100-mLvolumetric flasks 1mL,3mL,and 5mL,respectively,of Standard thymol solution,and add 0.25Nsodium hydroxide to make the final volume 5.0mL.Add 5.0mLof 0.25Nsodium hydroxide to a fourth flask in which the blank is to be prepared.To each flask add 10mLof Buffer solution,mix by gentle swirling,and add 1mLof Chlorimide solution.Allow to stand for 15minutes,accurately timed,add 3mLof 0.25Nsodium hydroxide to each flask,and add water to volume.With a suitable spectrophotometer,measure the absorbances of the thymol-containing solutions relative to the blank at 590nm.Plot the readings and draw the curve of best fit.
Procedure—
Place about 2mLof Halothane,accurately weighed,in a 100-mLvolumetric flask containing 5mLof 0.25Nsodium hydroxide,and mix by gentle swirling.Evaporate the halothane under a stream of nitrogen,and add 10mLof Buffer solutionand 1mLof Chlorimide solution.Swirl gently,allow to stand for 15minutes,accurately timed,add 3mLof 0.25Nsodium hydroxide,and add water to volume.Read the absorbance of the resulting solution,and by reference to the Standard thymol curve,calculate the percentage of thymol in the weight of Halothane taken.
Chromatographic purity—
Standard preparation—
Add 1.0µLof 1,1,2-trichloro-1,2,2-trifluoroethane to 20.0mLof the test specimen.
Chromatographic system—
Under typical conditions,the gas chromatograph is equipped with a flame-ionization detector,and contains a 3-m ×2-mm stainless steel column packed with 20%G24on support S1AB.The column is maintained at 60,the injection port and detector block are maintained at 200,and nitrogen is used as the carrier gas at a flow rate of about 15mLper minute.Typical retention times are about 5minutes for 1,1,2-trichloro-1,2,2-trifluoroethane and about 13minutes for halothane.
,the injection port and detector block are maintained at 200,and nitrogen is used as the carrier gas at a flow rate of about 15mLper minute.Typical retention times are about 5minutes for 1,1,2-trichloro-1,2,2-trifluoroethane and about 13minutes for halothane.
Procedure—
Inject separately equal volumes (about 2µL)of the Standard preparationand Halothane into a suitable gas chromatograph,and record the chromatograms.The total area of all peaks (except that of halothane)recorded for the test specimen does not exceed that due to the added 1,1,2-trichloro-1,2,2-trifluoroethane in the Standard preparation(0.005%).
Auxiliary Information—
Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 939
Phone Number:1-301-816-8379