Delivered dose uniformity over the entire contents:
meets the requirements for
Metered-Dose Inhalers under
Aerosols, Nasal Sprays, Metered-Dose Inhalers, and Dry Powder Inhalers 
601
.
PROCEDURE FOR DOSE UNIFORMITY—
Standard preparation—
Dissolve an accurately weighed quantity of
USP Epinephrine Bitartrate RS in a freshly prepared sodium bisulfite solution (1 in 500), and dilute quantitatively and stepwise with the same sodium bisulfite solution as necessary to obtain a solution having a known concentration of about 18 µg per mL.
Test preparation—
Discharge the minimum recommended dose into the sampling apparatus and detach the inhaler as directed. Rinse the apparatus (filter and interior) with four 5.0-mL portions of a freshly prepared sodium bisulfite solution (1 in 500), and transfer the resulting solutions quantitatively to a 50-mL centrifuge tube. Add 10 mL of chloroform, insert the stopper, shake vigorously for 1 minute, and centrifuge for 5 minutes. Use the clear supernatant as directed in the
Procedure.
Procedure—
Into three separate flasks, transfer the
Test preparation, 20.0 mL of the
Standard preparation, and 20.0 mL of water to provide the blank. To each flask add 100 µL of
Ferro-citrate solution and 1.0 mL of
Buffer solution, and mix. Concomitantly determine the absorbances with a suitable spectrophotometer, in 5-cm cells, of the solutions from the
Test preparation and the
Standard preparation, at the wavelength of maximum absorbance at about 530 nm, against the blank. Calculate the quantity, in µg, of C
9H
13NO
3 contained in the minimum dose taken by the formula:
(183.20 / 333.29)(20CN)(AU / AS),
in which
C is the concentration, in µg per mL, of
USP Epinephrine Bitartrate RS in the
Standard preparation; N is the number of sprays discharged to obtain the minimum recommended dose; 183.20 and 333.29 are the molecular weights of epinephrine and epinephrine bitartrate, respectively; and
AU and
AS are the absorbances of the solutions from the
Test preparation and the
Standard preparation, respectively.
Assay—
Weigh the Inhalation Aerosol, chill to a temperature below
30
, remove the valve by suitable means, and allow the Inhalation Aerosol to warm slowly to room temperature to expel the more volatile propellant fractions. Transfer the residues in the aerosol container and valve to a 125-mL separator with the aid of six 5-mL portions of dilute sulfuric acid (1 in 1000), and extract the solution with three 25-mL portions of chloroform. Proceed as directed in the
Assay under
Epinephrine Nasal Solution, beginning with “Rinse the stopper and mouth of the separator,” but use 10.0 mL instead of 5.0 mL of chloroform in the determination of the specific rotation. Dry the empty aerosol container and valve, weigh them, and determine the net weight of the Inhalation Aerosol. Calculate the quantity, in mg, of C
9H
13NO
3 in the Inhalation Aerosol taken by the formula:
(183.20 / 309.32)(W)(0.5 + 0.5R / 93),
in which 183.20 and 309.32 are the molecular weights of epinephrine and triacetylepinephrine, respectively, and
W is the weight, in mg, and
R is the specific rotation (in degrees, without regard to the sign), of the isolated triacetylepinephrine.
