Phendimetrazine Tartrate

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

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

DOWNLOAD PDF HERE

C₁₂H₁₇NO·C₄H₆O₆ 341.36

Morpholine, 3,4-dimethyl-2-phenyl-, (2S-trans)-, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1); (2S,3S)-3,4-Dimethyl-2-phenylmorpholine L-(+)-tartrate (1:1) CAS RN^®: 50-58-8; UNII: 6985IP0T80.

1 DEFINITION

Phendimetrazine Tartrate contains NLT 98.0% and NMT 102.0% of phendimetrazine tartrate (C₁₂H₁₇NO·C₄H₆O₆), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

Change to read:

B. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970 (CN 1-MAY-2020)

Sample solution: 1 mg/mL in methanol

Acceptance criteria: Meets the requirements

C. IDENTIFICATION TESTS-GENERAL, Tartrate (191)

3 ASSAY

PROCEDURE

Sample solution: Transfer an accurately weighed amount of 500 mg of Phendimetrazine Tartrate to a suitable beaker, and dissolve in 50 mL of glacial acetic acid.

Analysis: Add 1 drop of crystal violet TS to the Sample solution, and titrate with 0.1 N perchloric acid VS to a green endpoint. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 34.14 mg of phendimetrazine tartrate (C₁₂H₁₇NO·C₄H₆O₆).

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 CHLORIDE AND SULFATE, Chloride (221)

Sample: 1.0 g

Acceptance criteria: 0.035%; the Sample shows no more chloride than corresponds to 0.50 mL of 0.020 N hydrochloric acid.

4.3 CHLORIDE AND SULFATE, Sulfate (221)

Sample: 1.0 g

Acceptance criteria: 0.01%; the Sample shows no more sulfate than corresponds to 0.10 mL of 0.020 N sulfuric acid.

4.4 ORGANIC IMPURITIES

Standard solution: An aqueous solution containing 100 mg/mL of USP Phendimetrazine Tartrate RS

Sample solution: 100 mg/mL of Phendimetrazine Tartrate in water

Chromatographic system

(See Chromatography (621), Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 µL

Developing solvent system: Acetone, methanol, and ammonium hydroxide (50:50:1)

Analysis

Develop the chromatogram in a suitable chamber with the Developing solvent system until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, air-dry, view under short-wavelength UV light, and observe the location of the spots. Expose the plate to iodine vapors in a closed chamber.

Acceptance criteria: Yellow spots appear at the same locations as the spots observed under UV light, and the R_F value of the spot of the Sample solution corresponds to that of the Standard solution, and no other spot is obtained.

4.5 L-Erythro ISOMER

Sample solution: Dissolve 3.0 g of Phendimetrazine Tartrate in 25 mL of sodium hydroxide solution (1 in 20) in a suitable separator. Add 25 mL of sodium hydroxide solution (1 in 2), swirl, and allow the phendimetrazine base to separate. Discard the lower, alkaline layer, and collect the upper layer, centrifuging, if necessary, to obtain a clear liquid.

Chromatographic system

Mode: GC

Detector: Flame ionization

Column: 25-m x 0.25-mm capillary column, the inside wall of which is coated with a 0.4-µm film of liquid phase G1

Carrier gas: Helium

Temperatures

Injection port: 250°

Column: 140°

Detector: 280°

Injection volume: 1.0 µL

Injection type: Split ratio, 100:1

Analysis

Sample: Sample solution

[NOTE-The retention times for the D-threo isomer and the L-erythro isomer are about 8.5 and 9 min, respectively.]

Preferably using an electronic integrator, determine the areas of all peaks in the chromatogram.

Calculate the percentage of the L-erythro isomer in the Sample solution taken:

Result = (r_U/r_T) x 100

r_U = peak area of the L-erythro isomer peak

r_T = sum of the areas of the L-erythro isomer peak and the D-threo isomer peak

Acceptance criteria: NMT 0.1%

5 SPECIFIC TESTS

5.1 MELTING RANGE OR TEMPERATURE (741)

182°-188°, with decomposition, but the range between beginning and end of melting does not exceed 3°.

5.2 OPTICAL ROTATION, Specific Rotation(781S)

Sample solution: 100 mg/mL in water

Acceptance criteria: +32° to +36°

5.3 PH (791)

3.0-4.0, in a solution (1 in 40)

5.4 LOSS ON DRYING (731)

Analysis: Dry to constant weight at 105°.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers.

6.2 USP REFERENCE STANDARDS (11)

USP Phendimetrazine Tartrate RS