Tromethamine for Injection
»Tromethamine for Injection is a sterile,lyophilized mixture of tromethamine with Potassium Chloride and Sodium Chloride.It contains not less than 93.0percent and not more than 107.0percent of the labeled amount of tromethamine (C4H11NO3),and not less than 90.0percent and not more than 110.0percent of the labeled amounts of potassium chloride (KCl)and of sodium chloride (NaCl).
Packaging and storage— Preserve in Containers for Sterile Solidsas described under Injections á1ñ.
Constituted solution— At the time of use,it meets the requirements for Constituted Solutionsunder Injections á1ñ.
Identification—
A: The IRabsorption spectrum of a mineral oil dispersion of it exhibits maxima only at the same wavelengths as that of a similar preparation of USP Tromethamine RS.
B: Asolution,prepared as directed in the labeling,responds to the tests for Chloride á191ñ,for Sodium á191ñ,and for Potassium á191ñ.
Bacterial endotoxins á85ñ— It contains not more than 0.03USP Endotoxin Unit per mg of tromethamine.
pHá791ñ: between 10.0and 11.5,in a solution prepared as directed in the labeling.
Water,Method Iá921ñ— Add 5mLof glacial acetic acid prior to the titration:the content is not more than 1.0%.
Particulate matter á788ñ: meets the requirements for small-volume injections.
Potassium chloride content—
Standard solutions— Prepare five standard solutions (1,2,3,4,and 5)each containing 0.60mEq of sodium (35mg of sodium chloride)per liter,and to the solutions add,respectively,0-,2-,4-,6-,and 8-mg supplements of potassium,in the form of the chloride,per liter.If necessary,because of changes in the sensitivity of the photometer,vary the levels of concentration of the potassium,keeping the ratios between solutions approximately as given.
Standard graph— Set a suitable flame photometer for maximum emittance at a wavelength of 766nm to 767nm.(The exact wavelength setting will vary slightly with the instrument.)Adjust the instrument to zero emittance with solution 1.Then adjust the instrument to 100%emittance with solution 5.Read the percentage emittance of solutions 2,3,and 4.Plot the observed emittance of solutions 2,3,4,and 5as the ordinate and the concentration,in µg per mL,of potassium as the abscissa on arithmetic coordinate paper.
Procedure— Dissolve the entire contents of 1container of Tromethamine for Injection in sufficient water,and dilute quantitatively and stepwise with water to obtain a solution containing about 4µg of potassium per mL,or a quantity corresponding to the concentration of the Standard solutions.Adjust the instrument to zero emittance with solution 1and to 100%emittance with solution 5.Read the percentage emittance of the test solution.By reference to the Standard graph,determine the concentration,in µg per mL,of potassium in the test solution,apply the dilution factor,and calculate the quantity,in mg,of potassium in the container of Tromethamine for Injection.Each mg of potassium is equivalent to 1.907mg of potassium chloride (KCl).
Sodium chloride content— Proceed as directed under Potassium chloride content,with the following modifications:(1)Prepare the Standard solutionsto contain 0,2,4,6,and 8mg of sodium,in the form of the chloride,per 1000mL,without added potassium;(2)prepare the Standard graphwith the flame photometer set at 588nm to 589nm;and (3)under Procedureread “sodium”for “potassium”throughout.Each mg of sodium is equivalent to 2.542mg of sodium chloride (NaCl).
Other requirements— It meets the requirements for Sterility Tests á71ñ,Uniformity of Dosage Units á905ñ,and Labelingunder Injections á1ñ.
Assay for tromethamine— Dissolve the entire contents of 1container of Tromethamine for Injection in sufficient water,diluting with water to an accurately measured volume to obtain a solution containing about 36mg of tromethamine per mL.Transfer to a beaker an accurately measured volume of the solution,equivalent to about 180mg of tromethamine,dilute with water to about 100mL,add bromocresol purple TS,and titrate with 0.1Nhydrochloric acid VSto a yellow endpoint.Each mLof 0.1Nhydrochloric acid is equivalent to 12.11mg of C4H11NO3.
Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 1997
Phone Number:1-301-816-8389