Tranylcypromine Sulfate

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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(C₉H₁₁N)₂ · H₂SO₄            364.46

Cyclopropanamine, 2-phenyl-, trans-(+)-, sulfate (2:1);

(+)-trans-2-Phenylcyclopropylamine sulfate (2:1) CAS RN^®:13492-01-8; UNII: 7ZAT6ES870.

1 DEFINITION

Tranylcypromine Sulfate contains NLT 98.0% and NMT 102.0% of (C₉H₁₁N)₂ · H₂SO₄, calculated on the dried basis.

2 IDENTIFICATION

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

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

C. IDENTIFICATION TESTS-GENERAL, Sulfate (191): Meets the requirements

3 ASSAY

PROCEDURE

Buffer: Dissolve 3.4 g of monobasic ammonium phosphate in about 900 mL of water in a 1-L volumetric flask. Adjust with phosphoric acid to a pH of 2.2 ± 0.1, and dilute with water to volume.

Mobile phase: Methanol and Buffer (3:7)

0.05 N sulfuric acid: Cautiously add 1.3 ml. of sulfuric acid to 100 mL of water, cool to room temperature, and dilute to 1000 mL.

Diluent: Methanol, water, and 0.05 N sulfuric acid (1:3:1)

Standard stock solution: Using a sonicator, dissolve USP Tranylcypromine Sulfate RS in 0.05 N sulfuric acid and methanol (about 30% of the final volume of each solvent). Dilute with Diluent to obtain a 400 µg/mL solution.

Standard solution: 40 µg/mL of USP Tranylcypromine Sulfate RS in Diluent, prepared from the Standard stock solution

Sample stock solution: Using a sonicator, dissolve Tranylcypromine Sulfate in methanol and 0.05 N sulfuric acid (about 30% of the final volume of each solvent). Dilute with Diluent to obtain a 400 µg/mL solution.

Sample solution: 40 µg/mL tranylcypromine sulfate in Diluent, prepared from the Sample stock solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm x 25-cm; 4-um packing L11

Column temperature: 30°

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of (C₉H₁₁N)₂ · H₂SO₄ in the portion taken: 4

                          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 S

C_S = concentration of USP Tranylcypromine Sulfate RS in the Standard solution (µg/mL) 

C_U = concentration of tranylcypromine sulfate in the Sample solution (µg/mL) 

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 INORGANIC IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

4.2 ORGANIC IMPURITIES

PROCEDURE

Buffer, 0.05 N sulfuric acid, and Diluent: Proceed as directed in the Assay.

Solution A: Methanol and Buffer (3:17)

Solution B: Methanol and Buffer (3:7)

Mobile phase: See the gradient table below.

Standard stock solution: 14 µg/mL of USP Tranylcypromine Sulfate RS, and 60 µg/mL each of USP Tranylcypromine Related Compound A RS and USP Tranylcypromine Related Compound B RS in Diluent. [NOTE-Sonicate as needed.]

Standard solution: Transfer a portion of the Standard stock solution to a suitable volumetric flask containing methanol and 0.05 N sulfuric acid (30% of the final volume of each solvent). Dilute with Diluent to volume to obtain a solution containing 0.7 µg/mL of USP Tranylcypromine Sulfate RS and 3.0 µg/mL each of USP Tranylcypromine Related Compound A RS and USP Tranylcypromine Related Compound B RS.

Sample solution: Using a sonicator, dissolve Tranylcypromine Sulfate in methanol and 0.05 N sulfuric acid (about 30% of the final volume of each solvent). Dilute with Diluent to obtain a solution containing 680 µg/mL of tranylcypromine sulfate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 249 nm for tranylcypromine related compound B; 220 nm for all other specified and unspecified impurities

Column: 4.6-mm x 15-cm; 3-µm packing L1

Column temperature: 35°

Flow rate: 1.2 mL/min

Injection size: 25 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 2.0 between tranylcypromine and tranylcypromine related compound A, determined at 220 nm

Tailing factor: NMT 2.0 for tranylcypromine, determined at 220 nm

Relative standard deviation: NMT 6.0% for tranylcypromine and tranylcypromine related compound A, determined at 220 nm; NMT 6.0% for tranylcypromine related compound B, determined at 249 nm.

Analysis

Samples: Standard solution and Sample solution

[NOTE-Disregard the signal for tranylcypromine related compound B observed at 220 nm.)

Identify tranylcypromine related compound A, cis-hydrazide, trans-hydrazide, and any unspecified impurity using the data in Impurity, Table 1. Calculate the percentage of each impurity in the portion of sample taken:

                          Result = (r_U/r_S) × (C_S/C_U) × 100/F

r_U = peak response of the impurity from the Sample solution

r_S = peak response of the Standard solution S

C_S = concentration of USP Tranylcypromine Sulfate RS in the Standard solution (µg/mL)

C_U = concentration of Tranylcypromine Sulfate in the Sample solution (µg/mL)

F = response factor relative to tranylcypromine sulfate

Calculate the percentage of tranylcypromine related compound B in the portion of sample taken:

                          Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response at 249 nm of tranylcypromine related compound B from the Sample solution

r_S = peak response at 249 nm of tranylcypromine related compound B from the Standard solution

C_S = concentration of USP Tranylcypromine Related Compound B. RS in the Standard solution (µg/mL)

C_U = concentration of Tranylcypromine Sulfate in the Sample solution (µg/mL)

M_r1 = molecular weight of 3-phenylallylamine free base, 133.19

M_r2 = molecular weight of 3-phenylallylamine hydrochloride (USP Tranylcypromine Related Compound B RS), 169.66

Acceptance criteria

Individual impurities: See Impurity Table 1. [NOTE-Tranylcypromine related compound B is determined at 249 nm. All other specified and unspecified impurities are determined at 220 nm.]

Total impurities: NMT 1.0% for sum of tranylcypromine related compound A, tranylcypromine related compound B, cis-hydrazide, trans-hydrazide, and any unspecified impurity.

Impurity Table 1

^a (±)-cis-2-Phenylcyclopropanamine (cis-Cypromine).

^b 3-Phenylallylamine (Cinnamylamine), monitored at 249 nm.

^c (+)-cis-2-Phenylcyclopropanecarbohydrazide.

^d (±)-trans-2-Phenylcyclopropanecarbohydrazide.

5 SPECIFIC TESTS

LOSS ON DRYING (731): Dry a sample in vacuum at 60° for 2 h: it loses NMT 0.5% of its weight.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS (11)

USP Tranvicypromine Sulfate RS

USP Tranvleyeromine Related Compound. ARS

(+)-cis-2-Phenylcyclopropanamine hydrochloride; cis-tranylcypromine hydrochloride.

C₉H₁₁N · HCI            169.65

USP Tranvlcvpromine Related Compound B RS

3-Phenylallylamine hydrochloride; cinnamylamine hydrochloride.

C₉H₁₁N · HCI              169.65