Cetylpyridinium Chloride

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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C₂₁H₃₈ClN.H₂O 358.00 

C₂₁H₃₈ClN   339.99 

Pyridinium, 1-hexadecyl-, chloride, monohydrate; 

1-Hexadecylpyridinium chloride monohydrate CAS RN®: 6004-24-6. 

Anhydrous CAS RN®: 123-03-5. 

1 DEFINITION 

Cetylpyridinium Chloride contains NLT 98.0% and NMT 102.0% of cetylpyridinium chloride (C₂₁H₃₈ClN), calculated on the anhydrous basis. 

2 IDENTIFICATION 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K 

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. C. Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride 

Sample solution: 2 mg/mL in water 

Acceptance criteria: A 10-mL portion of the Sample solution meets the requirements of test A, except that when silver nitrate TS is added, turbidity is produced rather than a curdy white precipitate. 

3 ASSAY 

Procedure 

Use 0.1% trifluoroacetic acid–rinsed glassware and silanized vials for all solutions containing cetylpyridinium chloride, as cetylpyridinium may react with the surface. 

Solution A: Triuoroacetic acid and water (1:999) 

Solution B: Acetonitrile and triuoroacetic acid (999:1) 

Mobile phase: Solution A and Solution B (62.5:37.5) 

Standard solution: 0.25 mg/mL of USP Cetylpyridinium Chloride RS in Solution A 

Sample solution: 0.25 mg/mL of Cetylpyridinium Chloride in Solution A 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 258 nm 

Column: 2.1-mm × 10-cm; 5-µm packing L78 

Column temperature: 40° 

Flow rate: 0.6 mL/min 

Injection volume: 2 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 1.5 

Relative standard deviation: NMT 0.73% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of cetylpyridinium chloride (C₂₁H₃₈ClN) in the portion of Cetylpyridinium Chloride 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 Cetylpyridinium Chloride RS in the Standard solution (mg/mL)

C_U = concentration of Cetylpyridinium Chloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis 

4 IMPURITIES 

Residue on Ignition 〈281〉: NMT 0.2% on the anhydrous basis 

Change to read: 

Organic Impurities 

Use 0.1% trifluoroacetic acid–rinsed glassware and silanized vials for all solutions containing cetylpyridinium chloride, as cetylpyridinium may react with the surface. 

Solution A, Solution B, Mobile phase, and Chromatographic system: Proceed as directed in the Assay. 

Sensitivity solution: 1 µg/mL of USP Cetylpyridinium Chloride RS in Solution A (USP 1-May-2021) 

Standard solution: 2.5 µg/mL of USP Cetylpyridinium Chloride RSand 0.0125 mg/mL each of USP Myristylpyridinium Chloride RS and USP Stearylpyridinium Chloride RS (USP 1-May-2021) in Solution A 

Sample solution: 2.5 mg/mL of Cetylpyridinium Chloride in Solution A 

System suitability 

Samples: Sensitivity solution (USP 1-May-2021) and Standard solution 

Suitability requirements 

Relative standard deviation: NMT 2.0%,Standard solution 

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

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of myristylpyridinium chloride and stearylpyridinium chloride in the portion of Cetylpyridinium Chloride taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of myristylpyridinium or stearylpyridinium from the Sample solution

r_S = peak response of myristylpyridinium or stearylpyridinium from the Standard solution

C_S = concentration of USP Myristylpyridinium Chloride RS or USP Stearylpyridinium Chloride RS in the Standard solution (mg/mL)

C_U = concentration of Cetylpyridinium Chloride in the Sample solution (mg/mL) 

Calculate the percentage of each unspecified impurity in the portion of Cetylpyridinium Chloride taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

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

r_S = peak response of cetylpyridinium from the Standard solution 

C_S = concentration of USP Cetylpyridinium Chloride RS in in the Standard solution (mg/mL) 

C_U = concentration of Cetylpyridinium Chloride in the Sample solution (mg/mL) 

Acceptance criteria:  See Table 1. The reporting threshold is 0.05%. 

Table 1 

5 SPECIFIC TESTS 

Acidity 

Sample: 500 mg 

Analysis: Dissolve the Sample in 50 mL of water, add phenolphthalein TS, and titrate with 0.020 N sodium hydroxide. Acceptance criteria: NMT 2.5 mL is required for neutralization. 

Water Determination 〈921〉, Method I: 4.5%–5.5% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers. 

Change to read: 

USP Reference Standards 〈11〉 

USP Cetylpyridinium Chloride RS 

 USP Myristylpyridinium Chloride RS 

1-Tetradecylpyridinium chloride. 

C₁₉H₃₄ClN 311.94 

USP Stearylpyridinium Chloride RS 

1-Octadecylpyridinium chloride. 

C₂₃H₄₂ClN 368.0