Mirtazapine Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Mirtazapine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of mirtazapine (C₁₇H₁₉N₃).

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197

Extraction mixture: n-Hexane and water (1:1)

Sample: Transfer an amount equivalent to 30 mg of mirtazapine from finely powdered Tablets to a suitable centrifuge tube. Add Extraction mixture to obtain a solution of 1 mg/mL of mirtazapine in n-hexane. Shake for 5 min, and centrifuge. Decant, and evaporate the supernatant.

Standard: Dissolve USP Mirtazapine RS in Extraction mixture to obtain a solution having a concentration of about 1 mg/mL of mirtazapine in n-hexane. Shake for 5 min, and centrifuge. Decant, and evaporate the supernatant.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Diluent: Acetonitrile and water (1:1)

Buffer: Dissolve 18.0 g of tetramethylammonium hydroxide pentahydrate in 950 mL of water. Adjust with phosphoric acid to a pH of 7.4, and dilute with water to 1 L.

Mobile phase: Acetonitrile, methanol, tetrahydrofuran, and Buffer (15: 12.5:7.5:65)

Standard solution: 0.3 mg/mL of USP Mirtazapine RS in Diluent

Sample solution: Nominally 0.3 mg/mL of mirtazapine (from an amount equivalent to the weight of 1 Tablet from NLT 20 finely powdered Tablets) in Diluent. Shake vigorously for 10 min, centrifuge an aliquot, and use the clear supernatant.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 290 nm

Column: 4.6-mm x 25-cm; packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 7000 theoretical plates

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of mirtazapine (C₁₇H₁₉N₃) in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of USP Mirtazapine RS in the Standard solution (mg/mL)

C_u = nominal concentration of the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Sample solution: Pass a portion of the solution under test through a suitable lter. Dilute with Medium, if necessary.

Standard solution: USP Mirtazapine RS in Medium in a concentration similar to the one expected in the Sample solution

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 315 nm

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of the labeled amount of mirtazapine (C₁₇H₁₉N₃) dissolved:

Result = (A_u /A_s ) × C_s × V × (1/L) × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of USP Mirtazapine RS in the Standard solution (mg/mL)

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of mirtazapine (C₁₇H₁₉N₃) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

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

System suitability solution: 1.5 mg/mL of USP Mirtazapine Resolution Mixture RS in Diluent

Standard solution: 0.015 mg/mL of USP Mirtazapine RS in Diluent

Sample solution: 1.5 mg/mL of mirtazapine (from an amount equivalent to the weight of 1 Tablet from NLT 20 finely powdered Tablets) in Diluent. Shake vigorously for 10 min, centrifuge an aliquot, and use the clear supernatant.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm x 25-cm; packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: 2 times the retention time of mirtazapine

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times are listed in Table 1.]

Suitability requirements

Resolution: NLT 1.5 between acyclomirtazapine methyl derivative (impurity E) and 10-ketomirtazapine _{(ERR 1-Mar-2023)} (impurity F),

System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 10.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of any impurity from the Sample solution

r_s = mirtazapine peak response from the Standard solution

C_s = concentration of USP Mirtazapine RS in the Standard solution (mg/mL)

C_u = nominal concentration of the Sample solution (mg/mL)

F = relative response factor for the corresponding impurity (see Table 1)

Acceptance criteria: See Table 1.

Table 1

[Note—Disregard any peak representing less than 0.05% of the main peak and any peak that is due to the Diluent.]

^a 1,2,3,4,10,14b-Hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3-c][2]benzazepine 2-oxide. (Impurity A)

^b (2-(4-Methyl-2-phenylpiperazin-1-yl)pyridin-3-yl)methanol. (Impurity B)

^c (2-Methyl-3,4,10,14b-tetrahydrobenzo[c]pyrazino[1,2-a]pyrido[3,2-f]azepin-1(2H)-one. (Impurity C)

^d 1,2,3,4,10,14b-Hexahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepine. (Impurity D)

^e 4-Methyl-1-(3-methylpyridin-2-yl)-2-phenylpiperazine. (Impurity E)

^f 2-Methyl-1,2,3,4-tetrahydrobenzo[c]pyrazino[1,2-a]pyrido[3,2-f]azepin-10(14bH)-one. (Impurity F)

^g Process impurity. Included for identication purposes only. Not to be included in Total impurities.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers, and store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Mirtazapine RS

USP Mirtazapine Resolution Mixture RS

Mirtazapine.

Impurity A: 1,2,3,4,10,14b-Hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3-c][2]benzazepine 2-oxide.

Impurity B: (2-(4-Methyl-2-phenylpiperazin-1-yl)pyridin-3-yl)methanol.

Impurity C: (2-Methyl-3,4,10,14b-tetrahydrobenzo[c]pyrazino [1,2-a]pyrido[3,2-fazepin-1(2H)-one.

Impurity D: [NOTE-This impurity may be available either as the free base form or as the hydrochloride salt form.] 1,2,3,4,10,14b-Hexahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepine or 1,2,3,4,10,14b-Hexahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepine hydrochloride.

Impurity E: 4-Methyl-1-(3-methylpyridin-2-yl)-2-phenylpiperazine.

Impurity F: 2-Methyl-1,2,3,4-tetrahydrobenzo[c]pyrazino[1,2-a]pyrido[3,2-fjazepin-10(14bH)-one.