Polymyxin B Sulfate

Polymyxin B,sulfate.
Polymyxin Bsulfate [1405-20-5].
»Polymyxin B Sulfate is the sulfate salt of a kind of polymyxin,a substance produced by the growth of Bacillus polymyxa(Prazmowski)Migula (Fam.Bacillaceae),or a mixture of two or more such salts.It has a potency of not less than 6000Polymyxin B Units per mg,calculated on the dried basis.
Packaging and storage— Preserve in tight,light-resistant containers.
Labeling— Where packaged for prescription compounding,the label states the number of Polymyxin B Units in the container and per milligram,that it is not intended for manufacturing use,that it is not sterile,and that its potency cannot be assured for longer than 60days after opening.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 or other sterile dosage forms.
Identification—
A:Liquid Chromatographic Identification Test—
Mobile phase— Prepare a mixture of 0.1Mtribasic sodium phosphate and acetonitrile (77:23),and adjust with phosphoric acid to a pHof 3.0.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ.
Standard solution— Prepare a solution of USP Polymyxin B Sulfate RSin Mobile phasehaving a concentration of about 3.5mg per mL.Protect this solution from light.
Test solution— Prepare a solution of Polymyxin B Sulfate inMobile phasehaving a concentration of about 3.5mg per mL.Protect this solution from light.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 212-nm detector and a 4.6-mm ×25-cm column that contains 5-µm packing L1.The flow rate is about 1mLper minute.
Procedure— Separately inject equal volumes (about 10µL)of the Standard solutionand the Test solutioninto the chromatograph,and record the chromatograms.The chromatogram obtained from the Test solutioncorresponds qualitatively to that obtained from the Standard solution,exhibiting a major peak corresponding to polymyxin B1and peaks at relative retention times of about 0.5(polymyxin B2)and 0.6(polymyxin B3).
B: Dissolve 2mg in 5mLof water,add 5mLof 2.5Nsodium hydroxide,mix,and add 5drops of cupric sulfate solution (1in 100),shaking after the addition of each drop:a reddish violet color is produced.
C: Asolution (1in 20)meets the requirements of the tests for Sulfate á191ñ.
pHá791ñ: between 5.0and 7.5,in a solution containing 5mg per mL.
Loss on drying á731ñ— Dry about 100mg,accurately weighed,in a capillary-stoppered bottle in vacuum at 60for 3hours:it loses not more than 7.0%of its weight.
Content of phenylalanine— Transfer about 0.375g of Polymyxin B Sulfate,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with 0.1Nhydrochloric acid to volume,and mix.Measure the absorbances of this solution at the maxima at about 264nm (A264),258nm (A258),and 252nm (A252),and the absorbances at 280nm (A280)and 300nm (A300).Calculate the percentage of phenylalanine in the portion of Polymyxin B Sulfate taken by the formula:
(9.4787/W)(A258–0.5A252+0.5A264–1.84A280+0.8A300),
in which Wis the weight,in g,of Polymyxin B Sulfate taken:it contains between 9%and 12%of phenylalanine,calculated on the dried basis.
Other requirements— If for prescription compounding,it meets the requirements for Residue on ignitionunder Polymyxin Bfor Injection.Where the label states that Polymyxin B Sulfate is sterile,it meets the requirements for Sterility Tests á71ñand,where intended for injectable dosage forms,for Pyrogenunder Polymyxin Bfor Injection.Where the label states that Polymyxin B Sulfate must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements for Pyrogenunder Polymyxin Bfor Injection.
Assay— Proceed with Polymyxin B Sulfate as directed under Antibiotics—Microbial Assays á81ñ.
Auxiliary Information— Staff Liaison:William W.Wright,Ph.D.,Scientific Fellow
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 1576
Pharmacopeial Forum:Volume No.28(4)Page 1183
Phone Number:1-301-816-8335