Clioquinol

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₉H₅ClINO 305.50 

8-Quinolinol, 5-chloro-7-iodo-; 

5-Chloro-7-iodo-8-quinolinol CAS RN®: 130-26-7; UNII: 7BHQ856EJ5. 

1 DEFINITION 

Clioquinol, dried over phosphorus pentoxide for 5 h, contains NLT 93.0% and NMT 100.5% of clioquinol (C₉H₅ClINO). 

2 IDENTIFICATION 

A. 

Standard solution: Prepare as directed for the Standard solution in the Assay, except use 1.0 mL of pyridine instead of the Internal standard solution. 

Acceptance criteria: The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

Change to read: 

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Analytical wavelength: 267 nm 

Medium: 3 N hydrochloric acid 

Sample solution: 5 µg/mL 

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

C. 

Sample: 100 mg 

Analysis: Heat the Sample with 5 mL of sulfuric acid. 

Acceptance criteria: Copious violet vapors of iodine are evolved. 

3 ASSAY 

Procedure 

Internal standard solution: 2 mg/mL of pyrene in pyridine 

Standard stock solution: 3 mg/mL of USP Clioquinol RS in a mixture of pyridine and n-hexane (4:1) 

Standard solution: Transfer 1.0 mL of the Standard stock solution to a screw-capped glass vial fitted with a septum, add 1.0 mL of bis(trimethylsilyl)acetamide and 1.0 mL of Internal standard solution, attach the cap, and mix. Heat in a water bath at 50° for 15 min, and then cool to ambient temperature. 

Sample stock solution: 3 mg/mL of Clioquinol, previously dried, in a mixture of pyridine and n-hexane (4:1) 

Sample solution: Transfer 1.0 mL of the Sample stock solution to a screw-capped glass vial fitted with a septum, add 1.0 mL of bis(trimethylsilyl)acetamide and 1.0 mL of Internal standard solution, and attach the cap. Heat in a water bath at 50° for 15 min, and then cool to ambient temperature. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: GC 

Detector: Flame ionization 

Column: 1.83-m × 2-mm glass; packed with 3% liquid phase G3 on 80- to 100-mesh support S1AB 

Temperatures 

Column: The initial temperature is 200° for a conditioning period of NLT 16 h (not connected to the detector) and is then reduced to 165°. Injection port: 170° 

Detector: 250° 

Carrier gas: Helium 

Flow rate: 30 mL/min for helium. Hydrogen and air are introduced into the detector at rates of 25 and 500 mL/min, respectively. Injection volume: 1 µL 

System suitability 

Sample: Standard solution 

[Note—The relative retention times for clioquinol and pyrene are 0.6 and 1.0, respectively.] 

Suitability requirements 

Resolution: NLT 3 between the clioquinol and the internal standard peaks 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of clioquinol (C₉H₅ClINO) in the portion taken:  

Result = (R_U/R_S) × (C_S/C_U) × 100 

r_U = peak response ratio of clioquinol to the internal standard from the Sample solution

r_S = peak response ratio of clioquinol to the internal standard from the Standard solution

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

C_U = concentrationof clioquinol in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–100.5% 

4 IMPURITIES 

Residue on Ignition 〈281〉: NMT 0.5% 

5 SPECIFIC TESTS 

Loss on Drying 〈731〉 

Analysis: Dry a sample over phosphorus pentoxide for 5 h. 

Acceptance criteria: NMT 0.5% 

Free Iodine and Iodide 

Control solution: Dilute 2.0 mL of potassium iodide solution (1 in 6000) with water to 10 mL, add 6 mL of 2 N sulfuric acid, 1 mL of potassium dichromate TS, and 2 mL of chloroform, and shake for 15 s (0.05% of iodide). 

Sample: 1.0 g 

Analysis: 

Shake the Sample with 20 mL of water for 30 s, allow to stand for 5 min, and filter. To 10 mL of the filtrate add 1 mL of 2 N sulfuric acid, then add 2 mL of chloroform, and shake: no violet color appears in the chloroform (free iodine). To the mixture add 5 mL of 2 N sulfuric acid and 1 mL of potassium dichromate TS, and shake for 15 s. 

Acceptance criteria: The color of the chloroform layer is no deeper than that produced in the Control solution. 

6 ADDITIONAL REQUIREMENTS 

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

USP Reference Standards 〈11〉 

USP Clioquinol RS