A: Infrared Absorption 197K.

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.

Test solution: 10 mg per mL, in denatured alcohol.

Diluent: a mixture of methanol and water (85:15).

Test preparation— Dissolve 4.8 g of mirtazapine in 51 mL of methanol. Add 9 mL of water. Adjust 25 mL of this solution with 1 N acetic acid to a pH of between 3.0 and 4.0, using a short-range pH indicator paper as the internal indicator. Dilute with Diluent to 40 mL, and mix.

Diluent, Buffer solution, and Mobile phase— Proceed as directed in the Assay.

Standard solution— Dissolve an accurately weighed quantity of USP Mirtazapine RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 15 µg per mL.

Test solution— Transfer about 150 mg of Mirtazapine, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 240-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 40. Chromatograph the Standard solution, and record the peak response as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 10.0%.

Procedure— Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms for about twice the retention time of Mirtazapine, and measure the responses for the major peaks. Calculate the percentage of each impurity in the portion of Mirtazapine taken by the formula: in which F is the relative response factor for the mirtazapine impurities and is equal to 0.24 for 4-methyl-1-(3-methyl-pyridin-2-yl)-2-phenyl-piperazine at a relative retention time of about 1.3, and 1.0 for any other impurity; C is the concentration, in mg per mL, of USP Mirtazapine RS in the Standard solution; W is the weight, in mg, of Mirtazapine taken to prepare the Test solution; ri is the peak response of any impurity obtained from the Test solution; and rS is the mirtazapine peak response obtained from the Standard solution: not more than 0.1% of any individual impurity is found, and not more than 0.5% of total impurities is found. [NOTE—Disregard any peak representing less than 0.05% of the main peak and any peak that is due to the Diluent.]

(Official January 1, 2007)

Diluent: a mixture of acetonitrile and water (50:50).

Buffer solution— Transfer about 36.0 g of tetramethylammonium hydroxide pentahydrate to a 2000-mL volumetric flask, and dissolve in about 1950 mL of water. While stirring, adjust with phosphoric acid to a pH of 7.4, dilute with water to volume, and mix.

Mobile phase— Prepare a filtered and degassed mixture of Buffer solution, acetonitrile, methanol, and tetrahydrofuran (65:15:12.5:7.5). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of USP Mirtazapine RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 0.3 mg per mL.

Assay preparation— Transfer about 30 mg of Mirtazapine, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 290-nm detector and a 4.6-mm × 25-cm column that contains 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 response as directed for Procedure: the column efficiency is not less than 7000 theoretical plates; the tailing factor is not more than 2.0; and 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 responses for the major peaks. Calculate the quantity, in mg, of C17H19N3 in the portion of Mirtazapine taken by the formula: in which C is the concentration, in mg per mL, of USP Mirtazapine RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.