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.

Medium: 0.1 N hydrochloric acid; 900 mL.

Apparatus 2: 50 rpm.

Time: 15 minutes.

Procedure— Determine the amount of C17H19N3 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 315 nm on filtered portions of the solution under test, suitably diluted with Medium, in comparison with a Standard solution having a known concentration of USP Mirtazapine RS in the same Medium.

Tolerances— Not less than 80% (Q) of the labeled amount of C17H19N3 is dissolved in 15 minutes.

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

Standard stock solution— Prepare as directed for Standard preparation in the Assay under Mirtazapine.

Standard solution— Transfer 5.0 mL of the Standard stock solution to a 100-mL volumetric flask, dilute with Diluent to volume, and mix.

Test solution— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to the weight of 1 Tablet, to a suitable conical flask. Add Diluent to obtain a solution having a concentration of about 1.5 mg of mirtazapine per mL of Diluent. Shake vigorously for 10 minutes, centrifuge an aliquot, and use the clear supernatant.

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 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 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; V is the total volume, in mL, of the Test solution; C is the concentration, in mg per mL, of USP Mirtazapine RS in the Standard solution; W is the weight, in mg, of the powdered Tablets taken to prepare the Test solution; W20 is the weight of the 20 Tablets taken; L is the labeled amount, in mg, of mirtazapine in each Tablet; 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 0.2% of any individual impurity is found, and not more than 2.0% 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, Buffer solution, Mobile phase, and Standard preparation— Prepare as directed in the Assay under Mirtazapine.

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to the weight of 1 Tablet, to a suitable conical flask. Add Diluent to obtain a solution having a concentration of about 0.3 mg of mirtazapine per mL of Diluent. Shake vigorously for 10 minutes, centrifuge an aliquot, and use the clear supernatant.

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 1.5%.

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 responses for the major peaks. Calculate the quantity, in mg, of mirtazapine (C17H19N3) in the portion of Tablets taken by the formula: in which V is the volume, in mL, of the Assay preparation; 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.