Test specimen— To the contents of 1 vial of Nasal Spray add 1 mL of a saturated sodium chloride solution. Add 1 mL of a saturated solution of sodium carbonate, and shake vigorously for about 30 seconds. To the solution so obtained, add 2 mL of isopropyl alcohol, shake vigorously for about 30 seconds, and allow to stand until the phases separate. Transfer the organic phase to a suitable glass vial. Repeat the extraction with a second 2-mL portion of isopropyl alcohol, and transfer the organic phase to the same vial. Evaporate the solution under a stream of nitrogen. Dry the residue in an oven at 100º for 30 minutes, allow to cool to room temperature in a desiccator, and prepare a mull by the addition of 1 to 2 drops of mineral oil.

(W1 – W2)/D,

10 M Ammonium acetate solution— Dissolve 77.1 g of ammonium acetate in 100 mL of water.

Mobile phase— Prepare a filtered and degassed mixture of methanol and 10 M Ammonium acetate solution (9:1). Make adjustments if necessary (see System Suitability under Chromatography 621).

Diluent— Proceed as described in the Assay.

Standard solution— Dissolve an accurately weighed quantity of USP Sumatriptan Succinate Related Compound A RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 0.007 mg per mL (equivalent to about 0.005 mg per mL of C14H21N3O2S).

Test solution— Dissolve an appropriate volume of Nasal Spray in Diluent to obtain a solution having a concentration of about 1.0 mg of sumatriptan per mL.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 282-nm detector and a 4.6-mm × 20-cm column that contains packing L3. The flow rate is about 2.0 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 5%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of sumatriptan succinate related compound A in the portion of Nasal Spray taken by the formula: in which 495.7 and 613.8 are the molecular weights of sumatriptan related compound A and sumatriptan succinate related compound A, respectively; CS is the concentration, in mg per mL, of USP Sumatriptan Succinate Related Compound A RS in the Standard solution; CU is the concentration, in mg per mL, of sumatriptan in the Test solution; and rU and rS are the peak responses for sumatriptan related compound A from the Test solution and the Standard solution, respectively: Not more than 1.5% is found.

Diluent— Proceed as directed in the Assay.

Buffer solution— Dissolve about 1.7 mL of dibutylamine, about 0.6 mL of phosphoric acid, and about 3.9 g of monobasic sodium phosphate dihydrate in water. Adjust with a solution of 50% (w/v) sodium hydroxide to a pH of about 7.5, dilute with water to 1000 mL, and mix.

Mobile phase— Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (3:1). Make adjustments if necessary (see System Suitability under Chromatography 621).

System suitability solution— Dissolve accurately weighed quantities of USP Sumatriptan Succinate RS and USP Sumatriptan Succinate Related Compound C RS in Diluent to obtain a solution having known concentrations of about 1.4 mg per mL and 0.001 mg per mL, respectively.

Identification solution— Prepare a solution of USP Sumatriptan Succinate Related Impurities RS in Diluent having a concentration of about 3 mg per mL.

Test solution— Dissolve an appropriate volume of Nasal Spray in Diluent to obtain a solution having a concentration of about 1.0 mg of sumatriptan per mL.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 282-nm detector and a 4.6-mm × 20-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.9 for sumatriptan succinate related compound C and 1.0 for sumatriptan; and the resolution, R, between sumatriptan succinate related compound C and sumatriptan is not less than 1.5. Chromatograph the Identification solution, and record the peak responses as directed for Procedure: identify the peaks according to Table 1.

Procedure— Inject a volume (about 10 µL) of the Test solution into the chromatograph, record the chromatogram, and measure all of the peak responses. Calculate the percentage of each impurity in the portion of Nasal Spray taken by the formula: in which F is the relative response factor, which is equal to 2.89 for 1-[3-[2-dimethylamino)ethyl]-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-5-yl]-N-methylmethanesulfonamide that has a relative retention time of 0.46, 4.55 for 3a-hydroxy-1,1-dimethyl-5-{[(methylamino)sulfonyl]methyl}-1,2,3,3a,8,8a,hexahydropyrrolo[2,3-b]indol-1-ium that has a relative retention time of 0.64, and 1.0 for all other impurities; ri is the peak response for each impurity; and rs is the sum of the responses of all the peaks: not more than 1.5% of any impurity is found; and the total of all impurities, including the amount found in the test for Limit of sumatriptan related compound A, is not more than 4.0%.

(Official January 1, 2007)

Diluent— Dissolve 3.9 g of monobasic sodium phosphate dihydrate in water. Adjust with a solution of 50% (w/v) sodium hydroxide to a pH of about 6.5, and dilute with water to 1000 mL. Mix 750 mL of this solution with 250 mL of acetonitrile.

Buffer solution— Dissolve about 1.7 mL of dibutylamine, about 0.6 mL of phosphoric acid, and about 3.9 g of monobasic sodium phosphate dihydrate in water. Adjust with a solution of 50% (w/v) sodium hydroxide to a pH of about 6.5, dilute with water to 1000 mL, and mix.

Mobile phase— Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (3:1). Make adjustments if necessary (see System Suitability under Chromatography 621).

System suitability solution— Dissolve accurately weighed quantities of USP Sumatriptan Succinate RS and USP Sumatriptan Succinate Related Compound C RS in Diluent to obtain a solution having known concentrations of about 0.14 mg per mL and 0.07 mg per mL, respectively.

Standard preparation— Dissolve an accurately weighed quantity of USP Sumatriptan Succinate RS, and dissolve in Diluent to obtain a solution having a known concentration of about 0.14 mg per mL.

Assay preparation— Dissolve an appropriate volume of Nasal Spray in Diluent to obtain a solution having a known concentration of about 0.1 mg of sumatriptan per mL.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 282-nm detector and a 4.6-mm × 20-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.9 for sumatriptan succinate related compound C and 1.0 for sumatriptan; and the resolution, R, between sumatriptan succinate related compound C and sumatriptan 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 Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the amount of sumatriptan (C14H21N3O2S), in mg, in the portion of Nasal Spray taken by the formula: in which CS is the concentration, in mg per mL, of sumatriptan succinate in the Standard preparation; D is the dilution factor used in preparing the Assay preparation; and the other terms are as defined therein.