Phentermine Hydrochloride

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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C₁₀H₁₅N·HCI 185.69

Benzeneethanamine, α,α-dimethyl-, hydrochloride;

α,α-Dimethylphenethylamine hydrochloride CAS RN^®: 1197-21-3; UNII: 0K21505OTV.

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1 DEFINITION

Phentermine Hydrochloride contains NLT 98.0% and NMT 102.0% (USP 1-May-2022) of phentermine hydrochloride (C₁₀H₁₅N·HCI), calculated on the dried basis.

2 IDENTIFICATION

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A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K or 197A (USP 1-May-2022)

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B. The retention time of the phentermine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay (USP 1-May-2022)

C. IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests, Chloride: Meets the requirements

3 ASSAY

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3.1 PROCEDURE

Solution A: Dissolve 2.72 g of monobasic potassium phosphate in 1000 mL of water.

Mobile phase: Methanol and Solution A (55:45). Adjust with 50% (v/v) phosphoric acid in water to a pH of 2.4.

Standard solution: 0.1 mg/mL of USP Phentermine Hydrochloride RS in Mobile phase

Sample solution: 0.1 mg/mL of Phentermine Hydrochloride in Mobile phase

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 25-cm; 5-µm packing L7

Column temperature: 25°

Flow rate: 0.8 mL/min

Injection volume: 10 µL

Run time: NLT 8 times the retention time of phentermine

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

Relative standard deviation: NMT 0.73%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of phentermine hydrochloride (C₁₀H₁₅N·HCI) in the portion of Phentermine Hydrochloride taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of phentermine from the Sample solution

r_S = peak response of phentermine from the Standard solution

C_S = concentration of USP Phentermine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Phentermine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis (USP 1-May-2022)

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

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4.2 ORGANIC IMPURITIES

Buffer: 2 mg/mL of sodium 1-heptanesulfonate in water. Adjust with 25% (v/v) phosphoric acid in water to a pH of 2.3.

Mobile phase: Acetonitrile, methanol, and Buffer (20:25:55)

Diluent: Methanol and water (35:65)

Sensitivity solution: 0.5 µg/mL of USP Phentermine Hydrochloride RS in Diluent

Standard solution: 0.001 mg/mL each of USP Phentermine Hydrochloride RS and USP Phentermine Related Compound A RS in Diluent

Sample solution: 1 mg/mL of Phentermine Hydrochloride in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 45°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 10 times the retention time of phentermine

System suitability

Samples: Sensitivity solution and Standard solution

Suitability requirements

Resolution: NLT 3.0 between phentermine and phentermine related compound A, Standard solution

Relative standard deviation: NMT 5% for phentermine, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Phentermine Hydrochloride taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of phentermine from the Standard solution

C_S = concentration of USP Phentermine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Phentermine Hydrochloride in the Sample solution (mg/mL)

F = relative response factor of each impurity (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a 2-Methyl-1-phenylpropan-2-ol.

^b Result obtained in the test for Limit of Phentermine Related Compound C.

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4.3 LIMIT OF PHENTERMINE RELATED COMPOUND C

Buffer: Dissolve 4.04 g of sodium 1-heptanesulfonate in 1000 mL of water. Adjust with 25% (v/v) phosphoric acid in water to a pH of 2.3.

Mobile phase: Acetonitrile, methanol, and Buffer (50:25:25)

Sensitivity solution: 0.2 µg/mL of USP Phentermine Related Compound C RS in methanol

Standard solution: 0.001 mg/mL of USP Phentermine Related Compound C RS in methanol

Sample solution: 1 mg/mL of Phentermine Hydrochloride in methanol

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 45°

Flow rate: 1.2 mL/min

Injection volume: 10 µL

Run time: NLT 1.5 times the retention time of phentermine related compound C

System suitability

Samples: Sensitivity solution and Standard solution

Suitability requirements

Relative standard deviation: NMT 5%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of phentermine related compound C in the portion of Phentermine Hydrochloride taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of phentermine related compound C from the Sample solution

r_S = peak response of phentermine related compound C from the Standard solution

C_S = concentration of USP Phentermine Related Compound C RS in the Standard solution (mg/mL)

C_U = concentration of Phentermine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. (USP 1-May-2022)

5 SPECIFIC TESTS

5.1 MELTING RANGE OR TEMPERATURE (741)

202°-205°

5.2 PH (791)

Sample solution: 20 mg/mL of Phentermine Hydrochloride in water

Acceptance criteria: 5.0-6.0

5.3 LOSS ON DRYING (731)

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

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6.1 PACKAGING AND STORAGE

Preserve in tight containers. Store at 25°, excursions permitted between 15° and 30°.

(USP 1-May-2022)

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6.2 USP REFERENCE STANDARDS (11)

USP Phentermine Hydrochloride RS

USP Phentermine Related Compound A RS

N-(2-Methyl-1-phenylpropan-2-yl) formamide.

C₁₁H₁₅NO 177.25

USP Phentermine Related Compound C RS

(2-Methylprop-1-en-1-yl)benzene.

C₁₀H₁₂ 132.21 (USP 1-May-2022)