Acetylcysteine and Isoproterenol Hydrochloride Inhalation Solution
» Acetylcysteine and Isoproterenol Hydrochloride Inhalation Solution is a sterile solution of Acetylcysteine and Isoproterenol Hydrochloride in water. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of acetylcysteine (C5H9NO3S), and not less than 90.0 percent and not more than 115.0 percent of the labeled amount of isoproterenol hydrochloride (C11H17NO3·HCl).
Packaging and storage Preserve in single-dose or multiple-dose containers, preferably of Type I glass, tightly closed with a glass or polyethylene closure, and store at controlled room temperature.
Labeling The label indicates that the Inhalation Solution is not to be used if its color is pinkish or darker than slightly yellow or if it contains a precipitate.
USP Reference standards 11
USP Acetylcysteine RS.
USP Isoproterenol Hydrochloride RS. USP L-Phenylalanine RS.
Color and clarity Using the Inhalation Solution as the Test solution, proceed as directed for Color and clarity under Isoproterenol Inhalation Solution.
A: Place 2 mL in a 10-mL beaker, and adjust with 3 N hydrochloric acid to a pH of about 3 (pH indicator paper). Add 500 mg to 1 g of finely powdered sodium chloride, in two portions of about 200 mg each initially, and then in smaller portions (about 25 mg), stirring after each addition, until a precipitate is formed. Allow to stand at room temperature for 15 minutes, and collect the residue by suction filtration: the acetylcysteine so obtained, after being dried as directed in the test for Loss on drying under Acetylcysteine, responds to the Identification test under Acetylcysteine.
B: Ferro-Citrate Solution and Buffer SolutionPrepare as directed under Epinephrine Assay 391.
Procedure Place a volume of Inhalation Solution, equivalent to about 0.26 mg of isoproterenol hydrochloride, in a test tube with 3 mL of 0.1 M mercuric chloride, and mix. Add 100 µL of Ferro-Citrate Solution and 1.0 mL of Buffer Solution, and mix: the presence of isoproterenol hydrochloride is confirmed by the development of a purple color.
Sterility 71: meets the requirements.
pH 791: between 6.0 and 7.0.
Assay for acetylcysteine
Mobile phase, Internal standard solution, Standard preparation, and Chromatographic system Proceed as directed in the Assay under Acetylcysteine.
Assay preparation Pipet a volume of Inhalation Solution, equivalent to about 1000 mg of acetylcysteine, into a 100-mL volumetric flask, dilute with sodium metabisulfite solution (1 in 2000) to volume, and mix. Pipet 10 mL of this solution and 10 mL of Internal standard solution into a 200-mL volumetric flask, dilute with sodium metabisulfite solution (1 in 2000) to volume, and mix.
Procedure Proceed as directed for Procedure in the Assay under Acetylcysteine. Calculate the quantity, in mg, of C5H9NO3S in each mL of the Inhalation Solution taken by the formula:
2000(C/V)(RU / RS)in which C is the concentration, in mg per mL, of USP Acetylcysteine RS in the Standard preparation; V is the volume, in mL, of Inhalation Solution taken; and RU and RS are the ratios of the peak response of acetylcysteine to that of dl-phenylalanine obtained from the Assay preparation and the Standard preparation, respectively.
Assay for isoproterenol hydrochloride
Mobile phase Dissolve 13.6 g of monobasic potassium phosphate in 1000 mL of water, and pass through a membrane filter having a 0.45-µm porosity. Add 20.0 mL of methanol, mix, and degas.
Internal standard solution Place about 150 mg of acetaminophen in a 500-mL volumetric flask, add 5 mL of glacial acetic acid, dilute with water to volume, and mix.
Standard preparation Dissolve an accurately weighed quantity of USP Isoproterenol Hydrochloride RS in 0.05 M sodium metabisulfite to obtain a solution having a known concentration of 0.15 mg per mL. Transfer 10.0 mL of this solution to a 25-mL volumetric flask, add 10.0 mL of Internal standard solution, dilute with 0.2 M acetic acid to volume, and mix.
Assay preparation Transfer an accurately measured volume of Inhalation Solution, equivalent to about 1.5 mg of isoproterenol hydrochloride, and 10 mL of Internal standard solution to a 25-mL volumetric flask, add dilute glacial acetic acid (1 in 100) to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 40-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.5 for isoproterenol hydrochloride and 1.0 for acetaminophen; the resolution, R, between isoproterenol hydrochloride and acetaminophen is not less than 6; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 25 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 isoproterenol hydrochloride (C11H17NO3·HCl) in each mL of the Inhalation Solution taken by the formula:
(25C/V)(RU / RS)in which C is the concentration, in mg per mL, of USP Isoproterenol Hydrochloride RS in the Standard preparation; V is the volume, in mL, of Inhalation Solution taken; and RU and RS are the ratios of the peak responses of isoproterenol hydrochloride to those of acetaminophen obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information Please check for your question in the FAQs before contacting USP.Chromatographic Column
USP32NF27 Page 1424Pharmacopeial Forum: Volume No. 27(3) Page 2503
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.