A: Infrared Absorption 197M.

B: Ultraviolet Absorption 197U—

0.05 M Ammonium phosphate buffer, Mobile phase, System sensitivity solution, and Chromatographic system— Prepare as directed in the Assay.

Standard solution— Use the Standard preparation, prepared as directed in the Assay.

Test solution— Use the Assay preparation, prepared as directed in the Assay.

Procedure— Separately inject equal volumes (about 20 µL) of the Test solution and the Standard solution into the chromatograph, record the chromatogram for at least 2.5 times the retention time of orphenadrine citrate, and measure all of the peak areas. Calculate the percentage of each impurity in the portion of Orphenadrine Citrate taken by the formula: in which C is the concentration, in mg per mL, of USP Orphenadrine Citrate RS in the Standard solution; W is the weight, in mg, of the sample taken to prepare the Test solution; F is the relative response factor described in the table below; ri is the peak area for each impurity in the Test solution; and rS is the peak area of Orphenadrine Citrate in the Standard solution: not more than 0.5% of total impurities is found.

Solvent— Use carbon tetrachloride.

NMR reference— Use tetramethylsilane.

Test preparation— Place about 1 g of Orphenadrine Citrate and 10 mL of water in a 60-mL separator, slowly add about 20 drops of sodium hydroxide solution (1 in 2), with swirling, to obtain a solution having a pH of about 10, and extract with three 15-mL portions of ether. Combine the ether extracts in a beaker, discarding the aqueous phase, and evaporate to about one-half the volume by warming on a steam bath under a stream of nitrogen. Transfer to a 60-mL separator, wash with three 20-mL portions of water, and dry the ether solution with about 15 g of anhydrous sodium sulfate in a 125-mL conical flask for 1 hour, with intermittent swirling. Decant the dried ether solution through a pledget of glass wool into a small beaker. Rinse the sodium sulfate with two 10-mL portions of ether, and add the rinsings to the beaker. Evaporate most of the ether by warming under a stream of nitrogen, and remove the last traces of ether by drying at a pressure not exceeding 2 mm of mercury at 60. Transfer 400 mg of the orphenadrine so obtained to a small weighing bottle, add 0.5 mL of carbon tetrachloride and 1 drop of tetramethylsilane, and swirl to dissolve.

Procedure— Proceed as directed for Relative Method of Quantitation under Nuclear Magnetic Resonance 761, using the calculation formula given therein, in which A1 is the sum of the average areas of the combined methine peaks associated with the meta- and para-methylbenzyl isomers, appearing at about 5.23 ppm, and A2 is the area of the methine peak associated with the ortho-methylbenzyl isomer, appearing at about 5.47 ppm, with reference to the tetramethylsilane singlet at 0 ppm, and both n1 and n2 are equal to 1: the limit of combined meta- and para-methylbenzyl isomers is 3.0%.

(Official January 1, 2007)

0.05 M Ammonium phosphate buffer— Dissolve 5.8 g of monobasic ammonium phosphate in 1000 mL of water, and adjust with ammonium hydroxide or phosphoric acid to a pH of 7.9 ± 0.05.

Mobile phase— Prepare a filtered and degassed mixture of methanol, 0.05 M Ammonium phosphate buffer, and acetonitrile (9:8:3). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of USP Orphenadrine Citrate RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.9 mg per mL.

System sensitivity solution— Dilute a volume of the Standard preparation quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.00045 mg per mL.

Assay preparation— Transfer about 45 mg of Orphenadrine Citrate, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 40. Chromatograph the Standard preparation, and record the peak areas as directed for Procedure: the column efficiency is not less than 4500 theoretical plates; the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%. Chromatograph the System sensitivity solution, and record the peak areas as directed for Procedure: the signal-to-noise ratio is not less than 10.

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 peak areas for orphenadrine citrate. Calculate the quantity, in mg, of C18H23NO·C6H8O7 in the portion of Orphenadrine Citrate taken by the formula: in which C is the concentration, in mg per mL, of USP Orphenadrine Citrate RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.