NOTE—When performing assays and tests, store all standard, system suitability, and sample solutions in a cool place, protected from light.

A: Infrared Absorption 197M.

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

C: It meets the requirements of the test for dry chlorides under Chloride 191.

0.05 M Ammonium phosphate buffer— Dissolve 5.75 g of monobasic ammonium phosphate in 1000 mL of water, and adjust with phosphoric acid to a pH of 3.00 ± 0.05.

Solution A— Prepare a filtered and degassed mixture of 0.05 M Ammonium phosphate buffer and acetonitrile (97:3).

Solution B— Prepare a filtered and degassed mixture of 0.05 M Ammonium phosphate buffer and acetonitrile (4:1).

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).

Resolution solution— Dissolve an accurately weighed quantity of USP Naratriptan Resolution Mixture RS in water to obtain a solution having a known concentration of about 0.11 mg per mL.

Test solution— Dissolve an accurately weighed quantity of Naratriptan Hydrochloride in water to obtain a solution having a known concentration of about 0.11 mg per mL.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 225-nm detector and a 4.6-mm × 15-cm column that contains 4-µm packing L1. The column temperature is maintained at 40. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.04 for 2-[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl]ethanesulfonic acid methylamide (naratriptan related compound B) and 1.0 for naratriptan; and the resolution, R, between naratriptan and naratriptan related compound B is not less than 1.5.

Procedure— Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the areas for all of the peaks. Calculate the percentage of each impurity in the portion of Naratriptan Hydrochloride taken by the formula: in which F is the relative response factor (see the accompanying table for values) for each impurity; ri is the peak response for each impurity; and rN is the naratriptan peak response (see the accompanying table for limits). In addition to not exceeding the limits listed in the accompanying table, not more than 0.1% of any other individual impurity is found; and not more than 1.5% of total impurities is found.

Solvent— Use dimethyl sulfoxide.

(Official January 1, 2007)

0.01 M Triethylamine phosphate buffer— Dilute 0.6 mL of phosphoric acid with water to 900 mL, and adjust with triethylamine to a pH of 2.5.

Mobile phase— Prepare a filtered and degassed mixture of 0.01 M Triethylamine phosphate buffer and isopropyl alcohol (9:1). Make adjustments if necessary (see System Suitability under Chromatography 621).

Resolution solution— Dissolve accurately weighed quantities of USP Naratriptan Hydrochloride RS and USP Naratriptan Resolution Mixture RS in Mobile phase to obtain a solution having known concentrations of about 0.11 mg per mL and 0.11 µg per mL, respectively.

Standard preparation— Dissolve an accurately weighed quantity of USP Naratriptan Hydrochloride RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.11 mg per mL.

Assay preparation— Transfer about 11 mg of Naratriptan Hydrochloride, accurately weighed, to a 100-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 282-nm detector and a 4.6-mm × 15-cm column that contains 3-µm packing L11. The column temperature is maintained at 35. The flow rate is about 1.5 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.9 for 3-(1-methylpiperidin-4-yl)-1H-indole (naratriptan related compound A), 1.0 for naratriptan, and 1.1 for naratriptan related compound B; and the resolution, R, between naratriptan related compound A and naraptriptan and between naratriptan related compound B and naratriptan is not less than 1.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 1.5%.

Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of C17H25N3O2S·HCl in the portion of Naratriptan Hydrochloride taken by the formula: in which C is the concentration, in mg per mL, of USP Naratriptan Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.