Metoprolol Tartrate Injection
»Metoprolol Tartrate Injection is a sterile solution of Metoprolol Tartrate in Water for Injection.It contains Sodium Chloride as a tonicity-adjusting agent.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of metoprolol tartrate [(C15H25NO3)2·C4H6O6].
Packaging and storage— Preserve in single-dose,light-resistant containers,preferably of Type Ior Type IIglass.
Identification— Place a volume of Injection,equivalent to about 40mg of metoprolol tartrate,in a separator,add 4mLof dilute ammonium hydroxide (1in 3),and extract with 20mLof chloroform,filtering the chloroform extract through chloroform-pre-rinsed anhydrous sodium sulfate.Evaporate the chloroform to dryness,and place in a freezer to congeal the residue:the IRabsorption spectrum of a potassium bromide dispersion of the residue so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Metoprolol Tartrate RS.
Bacterial endotoxins á85ñ— It contains not more than 25.0USP Endotoxin Units per mg of metoprolol tartrate.
Sterility á71ñ— It meets the requirements when tested as directed for Membrane Filtrationunder Test for Sterility of the Product to be Examined.
pHá791ñ: between 5.0and 8.0.
Other requirements— It meets the requirements under Injections á1ñ.
Assay—
Mobile phase— Prepare a degassed solution by dissolving 961mg of 1-pentanesulfonic acid sodium salt (monohydrate)and 82mg of anhydrous sodium acetate in a mixture of 550mLof methanol and 470mLof water and adding 0.57mLof glacial acetic acid.
Internal standard solution— Dissolve USP Oxprenolol Hydrochloride RSin freshly prepared Mobile phaseto obtain a solution containing about 720µg per mL.
Sodium chloride solution— Dissolve 9.0g of sodium chloride in water to make 1000mL.
Standard preparation— Dissolve an accurately weighed quantity of USP Metoprolol Tartrate RSin Sodium chloride solutionto obtain a stock solution having a known concentration of about 1000µg per mL.Mix equal volumes,accurately measured,of this stock solution and of Internal standard solution.
Assay preparation— Dilute an accurately measured volume of Injection,if necessary,quantitatively with Sodium chloride solutionto obtain a stock solution having a concentration of about 1000µg per mL.Mix equal volumes,accurately measured,of this stock solution and of Internal standard solution.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1mLper minute.Chromatograph three replicate injections of the Standard preparation,and record the peak responses as directed under Procedure:the relative standard deviation is not more than 2.0%,and the resolution factor between metoprolol tartrate and oxprenolol hydrochloride is not less than 2.0.
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.The relative retention times are about 0.8for metoprolol tartrate and 1.0for oxprenolol hydrochloride.Calculate the quantity,in mg,of metoprolol tartrate [(C15H25NO3)2·C4H6O6]in each mLof the Injection taken by the formula:
(L/D)(C)(RU/RS),
in which Lis the labeled quantity,in mg,of metoprolol tartrate in the Injection;Dis the concentration,in µg per mL,of metoprolol tartrate in the Assay preparation,on the basis of the labeled quantity in each mLof Injection taken and the extent of dilution;Cis the concentration,in µg per mL,of USP Metoprolol Tartrate RSin the Standard preparation;and RUand RSare the peak response ratios of metoprolol tartrate to oxprenolol hydrochloride obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1281
Phone Number:1-301-816-8305