A: Infrared Absorption 197K.

B: The alkaline filtrate from the test for Specific rotation responds positively to the test for Tartrate 191.

Test solution— Prepare a sample solution of about 240 mg per mL in water. Make the solution slightly alkaline by adding concentrated ammonium hydroxide dropwise. Rub the wall of the vessel with a glass rod so that the base precipitates out. Filter the base under suction, wash with a little water and acetone, and dry at 105 for 2 hours. Prepare and measure a 50 mg per mL solution of base precipitate in 1 M hydrochloric acid.

Buffer solution— Dissolve 3.25 g of 1-octanesulfonic acid sodium salt monohydrate in 1 L of water. Adjust slowly with 3 M phosphoric acid to a pH of 2.8.

Solution A— Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (9:1).

Solution B— Prepare a filtered and degassed mixture of acetonitrile and Buffer solution (9:1).

Mobile Phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).

Diluent— Prepare a mixture of Solution A and Solution B (8:2).

System suitability solution— Dissolve accurately weighed quantities of USP Phenylephrine Hydrochloride RS and USP Norphenylephrine Hydrochloride RS in Diluent, and dilute quantitatively, and stepwise if necessary, to obtain a solution having known concentrations of about 1.0 mg per mL and 0.9 µg per mL, respectively.

Blank solution— Prepare a solution containing 0.8 mg per mL L(+)-tartaric acid in Diluent.

Test solution— Transfer 78 mg of Phenylephrine Bitartrate, accurately weighed, to a 50-mL volumetric flask. Dissolve in and dilute with Diluent to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 215-nm detector and a 4-mm × 5.5-cm column that contains packing L1. The column and injection port temperatures are maintained at 45 ± 2. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between norphenylephrine and (–)-phenylephrine is not less than 1.5; the tailing factor of (–)-phenylephrine is less than 1.8; and the relative standard deviation for replicate injections is not more than 5%.

Procedure— Separately inject equal volumes (about 4 µL) of the Blank solution and the Test solution into the chromatograph, record the chromatograms, and measure all of the peak responses. Calculate the percentage of each impurity in the portion of Phenylephrine Bitartrate taken by the formula: in which ri is the peak response for each impurity, and rs is the sum of the responses of all the peaks. [NOTE—Examine the chromatogram of the Blank solution for peaks and disregard any corresponding peaks observed in the chromatogram of the Test solution.] The limits of impurities are specified in the accompanying table.

(Official January 1, 2007)