Mirtazapine
Pyrazino[2,1-a]pyrido[2,3-c][2]benzazepine,1,2,3,4,10,14b-hexahydro-2-methyl-. 1,2,3,4,10,14b-Hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3-c][2]-benzazepine [85650-52-8]. » Mirtazapine contains not less than 98.0 percent and not more than 102.0 percent of C17H19N3, calculated on the anhydrous basis.
Packaging and storage
Preserve in tight containers, and store at controlled room temperature.
Labeling
Label it to indicate whether it is anhydrous or hemihydrate.
Identification
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.
Specific rotation 781S:
between +2 and 2.
Test solution:
10 mg per mL, in denatured alcohol.
Water, Method I 921:
not more than 1.0% for the anhydrous form and between 1.0% and 3.5% for the hemihydrate form.
Residue on ignition 281:
not more than 0.1%.
Heavy metals, Method II 231:
0.001%.
Chromatographic purity
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:
10,000F(C/W) (ri / rS)
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. [noteDisregard any peak representing less than 0.05% of the main peak and any peak that is due to the Diluent.]
Assay
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:
100C(rU / rS)
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.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 2989
Pharmacopeial Forum: Volume No. 34(4) Page 964
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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