A: Infrared Absorption 197K —Specimens are to be prepared using undried USP Galantamine Hydrobromide RS and the test article.

B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Resolution solution, as obtained in the Assay.

C: A solution of 7 mg per mL in water meets the requirement of the silver nitrate precipitate test for Bromide 191.

Standard stock solution— Transfer an accurately measured quantity of palladium reference stock solution (NIST traceable), and dilute quantitatively with water to obtain a solution having a known concentration of about 20 mg per L.

Aqua regia— Carefully mix under a hood hydrochloric acid and nitric acid (3:1).

Standard solutions— Quantitatively dilute suitable volumes of Standard stock solution to obtain solutions having known concentrations of 0.2, 1.0, and 2.0 mg per L of palladium. [note—It is recommended that the required volume of Standard stock solution be mixed with a volume of Aqua regia equivalent to 5% of the final volume followed by water to obtain each of the required Standard solutions.]

System suitability solution— Prepare a solution having a known concentration of 1.6 mg per L of palladium, as directed for Standard solutions.

Blank solution— Dilute 5 mL of Aqua regia with water to 100 mL.

Digestion blank solution— Prepare this solution following the procedure for Test solution, without the test article.

Test solution— Weigh accurately 1 g of Galantamine Hydrobromide. Transfer the sample into an appropriate digestion system, and digest using appropriate acids (e.g., nitric acid or mixtures of nitric acid and sulfuric acid and mixtures of nitric acid and hydrogen peroxide). After digestion, heat to dryness. Add 0.5 mL of Aqua regia and 2 mL of water. Warm gently to dissolve any residue. Allow to cool. Transfer quantitatively upon rinsing with several mL of water into a 10-mL volumetric flask, and dilute with water to volume.

Atomic absorption spectrophotometer system— Use a standard atomic absorption spectrophotometric system (see Spectrophotometry and Light Scattering 851) equipped with a palladium hollow-cathode lamp. Measure the absorbances in an air–acetylene flame at 247.6 nm (e.g., using a 0.2-nm slit width) of the Blank solution and the 0.2, 1.0, and 2.0 mg per L Standard solutions, and construct the calibration curve: the correlation coefficient must be not less than 0.99. Measure the absorbance of the System suitability solution, and calculate the concentration of the System suitability solution: the recovery is between 87.5% and 112.5% of the actual concentration.

Procedure— Measure the absorbance of the Digestion blank solution and the Test solution. Calculate the concentration of palladium in the Test solution using the calibration curve, after correcting appropriately for the absorbance of the Digestion blank solution and sample weight. Calculate the amount of palladium in the Galantamine Hydrobromide taken to prepare the Test solution: not more than 0.001% (w/w) of palladium is found.

Buffer solution, Solution A, Solution B, Mobile phase, Resolution solution, Diluent, andChromatographic system— Prepare as directed in the Assay.

Standard solution— Dilute the Standard preparation quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 5.0 µg per mL of galantamine hydrobromide.

Test solution— Use the Assay preparation.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, and record the chromatograms. Identify the impurities, based on the relative retention times given in Table 1, and measure the peak responses. [note—Ignore the peak due to bromide near the void volume and any peak below 0.05%. The approximate relative retention times in Table 1 are for peak identification purposes only.] Calculate the percentage of each of the galantamine hydrobromide related compounds in the portion of Galantamine Hydrobromide, taken on the dried basis, by the formula: in which CS and CU are the concentrations, in mg per mL, of Galantamine Hydrobromide in the Standard solution and the Test solution, respectively; rU is the peak response of each impurity obtained from the Test solution; rS is the peak response of galantamine hydrobromide obtained from the Standard solution; F is the relative response factor for each of the impurities relative to galantamine hydrobromide; and L is the loss on drying, in percent, as determined in the test for Loss on drying. The limits are given in Table 1.

Buffer solution— Dissolve 0.79 g of dibasic sodium phosphate dihydrate and 2.46 g of monobasic sodium phosphate anhydrous in 1 L of water.

Solution A— To 950 mL of the Buffer solution, pipet exactly 50 mL of methanol, and mix.

Solution B: acetonitrile.

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 water and methanol (95:5).

Resolution solution— Dissolve an accurately weighed quantity of USP Galantamine Hydrobromide Related Compounds Mixture RS in Diluent, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a concentration of about 1 mg per mL.

Standard preparation— Dissolve an accurately weighed quantity of USP Galantamine Hydrobromide RS in Diluent, and dilute with Diluent quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 1.0 mg per mL.

Assay preparation— Dissolve an accurately weighed quantity of Galantamine Hydrobromide in Diluent, and dilute with Diluent quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 1.0 mg per mL.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm × 10-cm column that contains 3.5-µm packing L1. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 55. The chromatograph is programmed as indicated in Table 2. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure. Identify the peaks using the relative retention times given in Table 1: the resolution, R, between galantamine and 6-hexahydrogalantamine is not less than 4.5; the tailing factor for galantamine hydrobromide is not more than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 1.0%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, and measure the responses for the galantamine hydrobromide peak. Calculate the quantity, in percent, of C17H21NO3·HBr in the portion of Galantamine Hydrobromide taken, by the formula: in which CS and CU are the concentrations of galantamine hydrobromide, in mg per mL, of the Standard preparation and the Assay preparation, respectively; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.