Phenylpropanolamine 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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C₉H₁₃NO · HCl 187.67

Benzenemethanol, α-(1-aminoethyl)-, hydrochloride, (R*,S*)-, (±);

(±)-Norephedrine hydrochloride CAS RN®: 154-41-6; UNII: 8D5I63UE1Q.

1 DEFINITION

Phenylpropanolamine Hydrochloride contains NLT 98.0% and NMT 101.0% of phenylpropanolamine hydrochloride (C₉H₁₃NO · HCl), 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: 197U (CN 1-May-2020)

Solution: 500 μg/mL

Medium: Water

Analytical wavelength: 256 nm

Acceptance criteria: Absorptivities, calculated on the dried basis, do not differ by more than 3.0%.

C. Melting Range or Temperature 〈741〉

Sample: Dissolve 1 g in 10 mL of water, add 10 mL of saturated sodium carbonate solution, and mix. Separate the precipitate by vacuum filtration, using a sintered-glass filter of medium pore size. Wash with three 5-mL portions of ice-cold water. Dry the crystals at 80° for 1 h.

Acceptance criteria: The Sample melts between 101° and 104°.

3 ASSAY

Procedure

Sample: 500 mg

Analysis: Dissolve the Sample in 50 mL of glacial acetic acid. Add 10 mL of mercuric acetate TS and 2 drops of crystal violet TS, 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 18.77 mg of phenylpropanolamine hydrochloride (C₉H₁₃NO · HCl).

Acceptance criteria: 98.0%–101.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

4.1 Limit of Cathinone Hydrochloride

Diluent: Dilute hydrochloric acid (1 in 120)

Standard solution: 100 μg/mL of USP Cathinone Hydrochloride RS in Diluent

Sample solution: 100 mg/mL of Phenylpropanolamine Hydrochloride in Diluent

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 285 nm

Cell: 1 cm

Blank: Diluent

Analysis: Concomitantly determine the absorbances of the Sample solution and the Standard solution, using the Blank.

Acceptance criteria: The absorbance of the Sample solution is NMT than that of the Standard solution (NMT 0.10%).

4.2 Limit of Amphetamine Hydrochloride

Mobile phase: Acetonitrile, phosphoric acid, triethylamine, and water (50:8:5:950)

System suitability solution: 5 μg/mL each of USP Phenylpropanolamine Hydrochloride RS and USP Dextroamphetamine Sulfate RS in water

Sample stock solution: 250 mg/mL of Phenylpropanolamine Hydrochloride in water. Sonicate if necessary.

Sample solution: 100 mg/mL of Phenylpropanolamine Hydrochloride in water from Sample stock solution

Amphetamine standard stock solution: 2.5 μg/mL of USP Dextroamphetamine Sulfate RS in water

Standard solution: 1 μg/mL of USP Dextroamphetamine Sulfate RS and 100 mg/mL of Phenylpropanolamine Hydrochloride in water from Amphetamine standard stock solution and Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 206 nm

Column: 4.6-mm × 25-cm; 5-μm base-deactivated packing L1

Flow rate: 1 mL/min

Injection volume: 5 μL

System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times for phenylpropanolamine and amphetamine are 1.0 and 2.1, respectively.]

Suitability requirements

Resolution: NLT 15 between phenylpropanolamine and amphetamine, System suitability solution

Column efficiency: NLT 10,000 theoretical plates, System suitability solution

Relative standard deviation: NMT 3.0% for amphetamine, Standard solution

Analysis

Samples: Sample solution and Standard solution

Record the chromatograms, and measure the responses at the locus of the amphetamine peak.

Calculate the percentage of amphetamine hydrochloride in the portion of Phenylpropanolamine Hydrochloride taken:

Result = [r_U/(r_S − r_U)] × (C_S/C_U) × (M_r1/M_r2) × 0.2

r_U = amphetamine peak response from the Sample solution

r_S = amphetamine peak response from the Standard solution

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

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

M_r1 = molecular weight of amphetamine hydrochloride, 171.67

M_r2 = molecular weight of amphetamine sulfate, 368.49

Acceptance criteria: NMT 0.001%

5 SPECIFIC TESTS

Melting Range or Temperature, Class I〈741〉: 191°–196°

pH 〈791〉

Sample solution: A solution (3 in 100)

Acceptance criteria: 4.2–5.5

Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Labeling: Label it to indicate that it is for veterinary use only.

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Cathinone Hydrochloride RS

α-Aminopropiophenone hydrochloride.

C₉H₁₁NO · HCl 185.65

USP Dextroamphetamine Sulfate RS

USP Phenylpropanolamine Hydrochloride RS