» Inamrinone Injection is a sterile solution of Inamrinone in Water for Injection, prepared with the aid of Lactic Acid. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of inamrinone (C10H9N3O).
[CautionInamrinone is a cardiotonic agent. ]
Packaging and storage Preserve in single-dose containers, preferably of Type I glass, protected from light. Store at room temperature.
USP Reference standards 11
USP Inamrinone Related Compound B RS
A: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
B: Transfer a volume of Injection, equivalent to about 50 mg of inamrinone, to a glass-stoppered container. Add about 2 g of 50- to 100-mesh sulfonic acid cation-exchange resin, and shake for about 2 minutes or until the supernatant becomes essentially colorless. Filter, and collect the filtrate in an arsine generator flask (see Apparatus under Arsenic 211). Add 5 mL of diluted sulfuric acid, and boil gently on a hot plate for 5 to 10 minutes. Cool to room temperature. Add 10 mL of potassium permanganate TS, attach the scrubber unit and absorber tube, and place the apparatus on a warm hot plate. Add 1 mL of indicator solution (freshly prepared by dissolving 250 mg of sodium nitroferricyanide in sufficient water to make 9 mL and mixing with 1 mL of morpholine) to the absorber tube. Heat gently, allowing the vapors to bubble through the indicator: the indicator turns blue within 5 minutes (presence of lactate).
Bacterial endotoxins 85 It contains not more than 0.5 USP Endotoxin Unit per mg of inamrinone.
pH 791: between 3.2 and 4.0.
Lactic acid content
Ion-exchange column Place a small pledget of glass wool at the bottom of a 100- × 6-mm glass column, equipped with a stopcock and a 25-mL reservoir. Soak a suitable quantity of 50- to 100-mesh sulfonic acid cation-exchange resin in 6 N hydrochloric acid for several minutes. Wash with water until the wash is neutral to wide-range pH indicator paper. Fill the column with the prepared resin to the base of the reservoir. Wash the column with about 50 mL of water in several portions, draining each wash to the top of the resin before adding the next portion. Discard the washes.
Procedure Place a 125-mL conical flask below the Ion-exchange column. Pipet a volume of Injection, equivalent to about 50 mg of inamrinone, onto the column. Allow the specimen to pass through the column at the rate of about 0.5 mL to 1 mL per minute, draining the specimen to the top of the column and collecting the eluate in the flask. Wash the column with five 5-mL portions of water, collecting the washings in the flask. Add several small glass beads to the solution in the flask, and boil on a hot plate for about 10 minutes. Add 10.0 mL of 0.1 N sodium hydroxide, and boil for 20 minutes. Add phenolphthalein TS, and titrate the warm solution with 0.1 N hydrochloric acid VS. Perform a blank determination (see Residual Titrations under Titrimetry 541). Each mL of 0.1 N hydrochloric acid is equivalent to 9.008 mg of C3H6O3: the lactic acid content is between 5.0 and 7.5 mg per mL of Injection.
Mobile phase Dilute 11.4 mL of phosphoric acid with water to 990 mL. Prepare a filtered and degassed mixture of the dilute phosphoric acid and acetonitrile (99:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution Transfer accurately weighed quantities of about 10 mg of USP Inamrinone RS and about 25 mg of USP Inamrinone Related Compound B RS to a 100-mL volumetric flask, add about 60 mL of lactic acid solution (1 in 85), and sonicate for about 2 minutes to effect solution. Cool, dilute with lactic acid solution (1 in 85) to volume, and mix. Pipet 10.0 mL of this solution into a 250-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Test solution Immediately before use, pipet a volume of Injection, equivalent to about 100 mg of inamrinone, into a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 313-nm detector and a 4-mm × 15-cm column that contains base-deactivated packing L7. The column temperature is maintained at a temperature between 30 and 35, and the flow rate is about 2 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the resolution, R, between inamrinone and inamrinone related compound B is not less than 10; and the relative standard deviation for replicate injections is not more than 10%.
Procedure Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas of the peak responses. Calculate the percentage of inamrinone related compound B relative to inamrinone in the volume of Injection taken by the formula:
5(C / W)(rU / rS)in which C is the concentration, in µg per mL, of USP Inamrinone Related Compound B RS in the Standard solution; W is the weight, in mg, of inamrinone in the volume of Injection taken; and rU and rS are the inamrinone related compound B peak responses obtained from the Test solution and the Standard solution, respectively. Separately calculate the percentage of any other impurity present in the volume of Injection taken by the formula:
5(C / W)(ri / rS)in which ri is the peak response for each impurity, and the other terms are as previously defined. Not more than 2.0% of inamrinone related compound B and not more than 0.5% of any other individual impurity is found, and the sum of all impurities is not more than 3.0%.
Other requirements It meets the requirements under Injections 1.
Assay [notePrepare all inamrinone-containing solutions immediately before injection into the chromatograph. ]
pH 7 sodium borate buffer , 0.5 MTransfer 31 g of boric acid to a beaker containing approximately 800 mL of water. Slowly add sodium hydroxide solution (1 in 5) in small quantities, stirring well after each addition, until all of the boric acid is dissolved and the pH is constant at 7.0 ± 0.3. Transfer this solution to a 1000-mL volumetric flask, dilute with water to volume, and mix.
Mobile phase Prepare a filtered and degassed mixture of water, methanol, and pH 7 sodium borate buffer, 0.5 M (500:480:20). Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution Dissolve accurately weighed quantities of USP Inamrinone RS and USP Inamrinone Related Compound C RS in Mobile phase to obtain a solution containing about 50 µg of each per mL.
Standard preparation Dissolve an accurately weighed quantity of USP Inamrinone RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 50 µg per mL.
Assay preparation Transfer an accurately measured volume of Injection, equivalent to about 5 mg of inamrinone, to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)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 1 mL per minute. Chromatograph the System suitability solution and the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are 0.6 for inamrinone related compound C and 1.0 for inamrinone; the resolution, R, between the inamrinone related compound C and inamrinone peaks is not less than 3; and the relative standard deviation for replicate injections of the Standard preparation is not more than 2.0%.
Procedure Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of amrinone (C10H9N3O) in each mL of the Injection taken by the formula:
(0.1C / V)(rU / rS)in which C is the concentration, in µg per mL, of USP Inamrinone RS in the Standard preparation; V is the volume, in mL, of Injection taken; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3485