Medium: water; 500 mL.

Apparatus 2: 50 rpm.

Time: 45 minutes.

Phosphate buffer-bromothymol blue solution— Dissolve 3.40 g of monobasic sodium phosphate in about 50 mL of water, add 18 mL of 0.1 N sodium hydroxide, dilute with water to 500 mL, and mix. Adjust the solution, if necessary, with 1 N sodium hydroxide or 1 N phosphoric acid (Buffer solution) to a pH of 5.8 ± 0.1. Mix 31.2 mg of bromothymol blue with 1.0 mL of 0.1 N sodium hydroxide, add Buffer solution to obtain 500 mL of solution, and mix.

Standard solution— Dissolve an accurately weighed quantity of USP Hydrocodone Bitartrate RS in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 10 µg per mL.

Test solution— Pipet into a 125-mL separator a volume of a filtered portion of the solution under test that is estimated to contain about 0.4 mg of hydrocodone bitartrate. Add 2 drops of 6 N ammonium hydroxide, and extract with three 25-mL portions of chloroform. Filter the extracts through about 3 g of anhydrous sodium sulfate supported on filter paper, and combine the filtered extracts in a 100-mL volumetric flask. Add chloroform through the filter to volume, and mix.

Procedure— Pipet 10 mL of the Standard solution into a 125-mL separator, and add 25.0 mL of chloroform. Pipet 25 mL of the Test solution into a second 125-mL separator, and add 10.0 mL of water. Pipet 25 mL of chloroform and 10 mL of water into a third 125-mL separator to provide a blank. Treat each mixture as follows. Add 30 mL of Phosphate buffer-bromothymol blue solution, and shake vigorously for not less than 15 minutes. Allow the layers to separate, and pass the chloroform layer through filter paper, discarding the first 10 mL of the filtrate. Determine the absorbances of the clear filtrates in 3-cm cells at the wavelength of maximum absorbance at about 415 nm, using the solution from the blank to set the spectrometer. Calculate the amount of C18H21NO3·C4H6O6·2½H2O dissolved by the formula: in which 494.50 and 449.46 are the molecular weights of the hydrated and anhydrous forms of hydrocodone bitartrate, respectively; CS is the concentration, in µg per mL, of USP Hydrocodone Bitartrate RS in the Standard solution; VU is the volume of the filtered solution under test that is estimated to contain 0.4 mg of hydrocodone bitartrate; and AU and AS are the absorbances of the solutions from the Test solution and the Standard solution, respectively.

Tolerances— Not less than 75% (Q) of the labeled amount of C18H21NO3·C4H6O6·2½H2O is dissolved in 45 minutes.

Procedure for content uniformity— Transfer 1 finely powdered Tablet to a 50-mL volumetric flask, add 0.1 N sulfuric acid to volume, and mix. Filter if necessary, discarding the first 20 mL of the filtrate. Concomitantly determine the absorbances of this solution and a solution of USP Hydrocodone Bitartrate RS in the same medium, having a known concentration of about 100 µg per mL, in 1-cm cells at the wavelength of maximum absorbance at about 280 nm, with a suitable spectrophotometer, using 0.1 N sulfuric acid as the blank. Calculate the quantity, in mg, of C18H21NO3·C4H6O6·2 ½H2O in the Tablet taken by the formula: in which 494.49 and 449.46 are the molecular weights of the hydrated and anhydrous forms of hydrocodone bitartrate, respectively; T is the labeled quantity, in mg, of hydrocodone bitartrate in the Tablet; C is the concentration, in µg per mL, of USP Hydrocodone Bitartrate RS in the Standard solution; D is the concentration, in µg per mL, of the solution from the Tablet, based upon the labeled quantity per Tablet and the extent of dilution; and AU and AS are the absorbances of the solution from the Tablet and the Standard solution, respectively.

(Official January 1, 2007)