Promethazine 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 

Promethazine Hydrochloride Injection is a sterile solution of Promethazine Hydrochloride in Water for Injection. It contains NLT 95.0% and NMT 110.0% of the labeled amount of promethazine hydrochloride (C₁₇H₂₀N₂S .HCl). 

[Note—Throughout the following procedures, protect the samples, the Reference Standards, and the solutions containing them, by conducting the procedures without delay under subdued light or using low-actinic glassware.] 

2 IDENTIFICATION 

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

3 ASSAY 

Procedure 

Buffer: 3.7 g/L of ammonium acetate in water Solution A: Acetonitrile and Buffer (30:70) Mobile phase: See Table 1. 

Table 1 

Diluent: 0.1% triethylamine in methanol 

System suitability solution: 1.0 µg/mL each of USP Promethazine Hydrochloride RS and USP Promethazine Related Compound B RS in Diluent 

Standard solution: 0.05 mg/mL of USP Promethazine Hydrochloride RS in Diluent 

Sample solution: Nominally 0.05 mg/mL of promethazine hydrochloride from a volume of Injection in Diluent [Note—Sonication may be used in the preparation of System suitability solution, Standard solution, and Sample solution.] Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm. For identification B, use a diode array detector in the range of 200–400 nm. 

Column: 4.6-mm × 15-cm; 5-μm packing L1 

Temperatures 

Column: 30° 

Autosampler: 4° 

Flow rate: 1.4 mL/min 

Injection volume: 15 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for promethazine and promethazine related compound B are 1.0 and 1.3, respectively.] Suitability requirements 

Resolution: NLT 5.0 between the promethazine and promethazine related compound B peaks, System suitability solution Tailing factor: NMT 2.0, Standard solution 

Relative standard deviation: NMT 1.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of promethazine hydrochloride (C₁₇H₂₀N₂S .HCl) in the portion of Injection taken: 

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 

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

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

Acceptance criteria: 95.0%–110.0% 

4 IMPURITIES

Organic Impurities 

Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay. 

Standard solution: 1.0 µg/mL each of USP Promethazine Hydrochloride RS and USP Promethazine Related Compound B RS in Diluent Sample solution: Nominally 500 µg/mL of promethazine hydrochloride from a volume of Injection in Diluent [Note—Sonication may be used in the preparation of Standard solution and Sample solution.] 

System suitability 

Sample: Standard solution 

[Note—See Table 2 for the relative retention times.] 

Suitability requirements 

Resolution: NLT 5.0 between the promethazine and promethazine related compound B peaks 

Relative standard deviation: NMT 2.0% for promethazine 

Analysis 

Samples: Standard solution and Sample solution 

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

Result = (r_U/r ) × (C /C_U) × (1/F) × 100 

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

r_S = peak response of promethazine from the Standard solution 

C_S = concentration of USP Promethazine Hydrochloride RS in the Standard solution (µg/mL) 

C_U = nominal concentration of promethazine hydrochloride in the Sample solution (µg/mL) 

F = relative response factor (see Table 2) 

Acceptance criteria: See Table 2. Disregard peaks less than 0.05%. 

Table 2 

aN,N-Dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amine sulfoxide.

b N-Methyl-1-(10H-phenothiazin-10-yl)propan-2-amine. 

c This is a process impurity that is controlled in the drug substance and is included for identification only. 

d 10H-Phenothiazine. 

5 SPECIFIC TESTS 

Bacterial Endotoxins Test 〈85〉: NMT 5.0 USP Endotoxin Units/mg of promethazine hydrochloride 

pH 〈791〉: 4.0–5.5 

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

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in single-dose or in multiple-dose containers, preferably of Type I glass, protected from light. USP Reference Standards 〈11〉 

USP Promethazine Hydrochloride RS 

USP Promethazine Related Compound B RS 

Isopromethazine hydrochloride; 

N,N-Dimethyl-2-(10H-phenothiazin-10-yl)propan-1-amine hydrochloride. 

C₁₇H₂₀N₂S .HCl 320.88