A: Infrared Absorption 197K.

B: Ultraviolet Absorption 197U—

Solution A: water.

Solution B— Prepare a filtered and degassed mixture of acetonitrile, water, and triethylamine (160:40:1). Adjust with phosphoric acid to a pH of 7.0.

Diluent— Prepare a mixture of 0.1 N sodium hydroxide solution and methanol (75:25).

Blank solution— Prepare a mixture of Diluent and methanol (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).

Resolution solution— Dissolve 5 mg each of USP Lansoprazole RS and USP Lansoprazole Related Compound A RS in 200 mL of methanol. Pipet 1 mL of this solution into a 10-mL volumetric flask, dilute with Diluent to volume, and mix.

System suitability solution— Dissolve a suitable quantity of USP Lansoprazole Related Compound A RS in methanol, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.025 mg per mL. Pipet 1 mL of this solution into a 10-mL volumetric flask, dilute with Diluent to volume, and mix.

Standard solution— Dissolve an accurately weighed quantity of USP Lansoprazole RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 25 µg per mL. Pipet 1 mL of this solution into a 10-mL volumetric flask, dilute with Diluent to volume, and mix. The final concentration of the Standard solution is about 2.5 µg per mL.

Test solution— Transfer about 125 mg of Lansoprazole, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with methanol to volume, and mix. Pipet 1 mL of this solution into a 10-mL volumetric flask, and dilute with Diluent to volume.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 285-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 0.8 mL per minute. The chromatograph is programmed as follows. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between lansoprazole and lansoprazole related compound A is not less than 6. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 3%.

Procedure— Separately inject equal volumes (about 40 µL) of the Blank solution, the Standard solution and the Test solution into the chromatograph, record the chromatograms, and identify the lansoprazole peak and the peaks due to the impurities listed in Table 1. Measure the areas for the major peaks, excluding the peaks obtained from the Blank solution. Calculate the percentage of each impurity in the portion of Lansoprazole taken by the formula: in which F is the relative response factor for each impurity peak (see Table 1 for values); 0.001 is the conversion factor from µg per mL to mg per mL; CS is the concentration, in µg per mL, of USP Lansoprazole RS in the Standard solution; CT is the concentration, in mg per mL, of Lansoprazole in the Test solution; ri is the peak response for each impurity obtained from the Test solution; and rS is the peak response for lansoprazole obtained from the Standard solution: In addition to not exceeding the limits for impurities in Table 1, not more than 0.6% of total impurities is found. Disregard any peak below 0.05%.

Diluent— Prepare a mixture of water, acetonitrile, and triethylamine (60:40:1), and adjust with phosphoric acid to a pH of 10.0.

Mobile phase— Prepare a filtered and degassed mixture of water, acetonitrile, and triethylamine (60:40:1). Adjust with phosphoric acid to a pH of 7.0. Make adjustments if necessary (see System Suitability under Chromatography 621).

Resolution solution— Dissolve suitable quantities of USP Lansoprazole RS and USP Lansoprazole Related Compound A RS in Diluent to obtain a solution containing about 0.1 mg of each per mL.

Internal standard solution— Dissolve an accurately weighed quantity of 4¢-ethoxyacetophenone in Diluent to obtain a solution having a known concentration of about 2.5 mg per mL.

Standard preparation— Dissolve an accurately weighed quantity of USP Lansoprazole RS in Internal standard solution to obtain a solution having a known concentration of about 5.0 mg per mL. Transfer 1.0 mL of this solution to a 50-mL volumetric flask, dilute with Diluent to volume, and mix.

Assay preparation— Transfer about 50 mg of Lansoprazole, accurately weighed, to a 10-mL volumetric flask, dissolve in and dilute with Internal standard solution to volume, and mix. Transfer 1.0 mL of this solution to a 50-mL volumetric flask, dilute with Diluent to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 285-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between lansoprazole and lansoprazole related compound A is not less than 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 1.0%.

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 peak responses. Calculate the percentage of C16H14F3N3O2S in the portion of Lansoprazole taken by the formula: in which CS and CU are the concentrations, in mg per mL, of lansoprazole in the Standard preparation and the Assay preparation, respectively; and RU and RS are the peak response ratios obtained from the Assay preparation and the Standard preparation, respectively.