Phenylephrine Hydrochloride Injection

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

Phenylephrine Hydrochloride Injection is a sterile solution of Phenylephrine Hydrochloride in Water for Injection. It contains NLT 90.0% and NMT 115.0% of the labeled amount of phenylephrine hydrochloride (C₉H₁₃NO₂ · HCl).

2 IDENTIFICATION

Change to read:

A. The retention time of the phenylephrine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1-Aug-2019)

Add the following:

B. The UV absorption spectrum of the phenylephrine peak of the Sample solution exhibits maxima and minima at the same wavelengths as those of the Standard solution, as obtained in the Assay.(USP 1-Aug-2019)

3 ASSAY

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Procedure

Solution A: Phosphoric acid and water (1:1000)

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard solution: 0.1 mg/mL of USP Phenylephrine Hydrochloride RS in water

Sample solution: Nominally 0.1 mg/mL of phenylephrine hydrochloride in water from a volume of Injection

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 273 nm. For Identification B, use a diode array detector in the range of 245–400 nm.

Column: 4.6-mm × 15-cm; 2.6-μm packing L1

Column temperature: 35°

Flow rate: 1.0 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of phenylephrine hydrochloride (C₉H₁₃NO₂ · HCl) in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of phenylephrine from the Sample solution

r_S = peak response of phenylephrine from the Standard solution

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

C_U = nominal concentration of phenylephrine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–115.0%

4 IMPURITIES

Add the following:

Organic Impurities

Solution A, Solution B, Mobile phase, and Sample solution: Prepare as directed in the Assay.

System suitability solution: 0.1 mg/mL of USP Phenylephrine Hydrochloride RS and 0.005 mg/mL of USP Phenylephrine Related Compound F RS in water

Sensitivity solution: 0.1 μg/mL of USP Phenylephrine Hydrochloride RS in water

Standard solution: 0.0002 mg/mL of USP Phenylephrine Hydrochloride RS in water

Chromatographic system: Proceed as directed in the Assay, except for the Detector.

Detector: UV 215 nm

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[Note - The relative retention times for phenylephrine related compound F and phenylephrine are 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between phenylephrine and phenylephrine related compound F, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

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

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each degradation product in the portion of Injection taken:

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

r_U = peak response of each degradation product from the Sample solution

r_S = peak response of phenylephrine from the Standard solution

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

C_U = nominal concentration of phenylephrine hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a 1-(3-Hydroxyphenyl)-2-(methylamino)ethan-1-one hydrochloride.

^b 2-Hydroxy-2-(2-{[(R)-2-hydroxy-2-(3-hydroxyphenyl)ethyl](methyl)amino}-2-oxoethyl)succinic acid.

5 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: It contains NMT 25.0 USP Endotoxin Units/mg of phenylephrine hydrochloride.

pH 〈791〉: 3.0–6.5

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass, protected from light. Store at controlled room temperature. (USP 1-Aug-2019)

Change to read:

USP Reference Standards 〈11〉

USP Phenylephrine Hydrochloride RS

USP Phenylephrine Related Compound F RS

(R)-2-Methyl-1,2,3,4-tetrahydroisoquinoline-4,8-diol hydrochloride monohydrate.

C₁₀H₁₃NO₂ · HCl · H₂O