Dexmedetomidine 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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1 DEFINITION 

Dexmedetomidine Hydrochloride contains NLT 98.0% and NMT 102.0% of dexmedetomidine hydrochloride (C₁₃H₁₆N₂ . HCl), calculated on the dried basis. 

2 IDENTIFICATION

Change to read: 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020) 

B. The retention time of the major peak of the Sample solution corresponds to that of the System suitability solution, as obtained in the test for Enantiomeric Purity. 

C. Identification Tests—General, Chloride 〈191〉: Meets the requirements 

3 ASSAY 

3.1 Procedure 

Buffer: 0.89 g/L dibasic sodium phosphate dihydrate solution prepared as follows. Dissolve a suitable amount of dibasic sodium phosphate dihydrate with 90% of total volume of water, adjust with 16 g/L of monobasic sodium phosphate dihydrate solution in water to a pH of 7.0, and dilute with water to volume. 

Mobile phase: Methanol and Buffer (60:40) 

Standard solution: 0.2 mg/mL of USP Dexmedetomidine Hydrochloride RS in Mobile phase 

Sample solution: 0.2 mg/mL of Dexmedetomidine Hydrochloride in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

Column: 4-mm × 12.5-cm; 5-µm packing L1 

Flow rate: 1 mL/min 

Injection volume: 20 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Relative standard deviation: NMT 0.73% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of dexmedetomidine hydrochloride (C₁₃H₁₆N₂ . HCl) in the portion of the sample taken: 

Result = (r_u/r_s) x (C_s/C_u) × 100 

r_u = peak response of dexmedetomidine from the Sample solution 

r_s = peak response of dexmedetomidine from the Standard solution 

C_s = concentration of USP Dexmedetomidine Hydrochloride RS in the Standard solution (mg/mL) 

C_u = concentration of Dexmedetomidine Hydrochloride in the Sample solution (mg/mL) 

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

4 IMPURITIES 

4.1 Residue on Ignition 〈281〉: NMT 0.1% 

4.2 Organic Impurities 

Buffer and Mobile phase: Proceed as directed in the Assay. 

Standard solution: 2 µg/mL of USP Dexmedetomidine Hydrochloride RS in Mobile phase 

Sensitivity solution: 0.8 µg/mL of USP Dexmedetomidine Hydrochloride RS in Mobile phase 

Sample solution: 2 mg/mL of sample in Mobile phase 

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

Run time: NLT 9 times the retention time of the dexmedetomidine peak 

System suitability 

Samples: Sensitivity solution and Standard solution 

Suitability requirements 

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

Relative standard deviation: NMT 5%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

[Note—The relative retention times of known impurities are given in Table 1.] 

Table 1 

a 1-(2,3-Dimethylphenyl)-1-(1H-imidazol-5-yl)ethanol. 

b 1-(1-Benzyl-1H-imidazol-5-yl)-1-(2,3-dimethylphenyl)ethanol. 

c 5-[1-(2,3-Dimethylphenyl)ethyl]-1-ethyl-1H-imidazole. 

d 1-Benzyl-5-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole. 

e 1-Benzyl-5-[1-(2,3-dimethylphenyl)vinyl]-1H-imidazole. 

Calculate the percentage of each impurity in the portion of the sample taken: 

Result = (r_u/r_s) x (C_s/C_u) x 100 

r_u = peak response of each impurity from the Sample solution 

r_s = peak response of dexmedetomidine in the Standard solution  

C_s = concentration of USP Dexmedetomidine Hydrochloride RS in the Standard solution (µg/mL) 

C_u = concentration of Dexmedetomidine Hydrochloride in the Sample solution (µg/mL) 

Acceptance criteria: Disregard peaks below 0.04%. 

Individual impurities: NMT 0.10% 

Total impurities: NMT 0.3% 

4.3 Enantiomeric Purity 

Buffer: To 1 L of 5.34 g/L dibasic sodium phosphate dihydrate solution, adjust with a suitable amount (about 700–800 mL) of 4.08 g/L monobasic potassium phosphate solution to a pH of 7.0. 

Mobile phase: Acetonitrile and Buffer (35:165) 

System suitability solution: 1 µg/mL of USP Levomedetomidine RS and 50 µg/mL of USP Dexmedetomidine Hydrochloride RS in Mobile phase 

Standard solution: 0.5 µg/mL of USP Levomedetomidine RS in Mobile phase 

Sensitivity solution: 0.05 µg/mL of USP Levomedetomidine RS in Mobile phase 

Sample solution: 50 µg/mL of sample in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

Column: 4-mm × 10-cm; 5-µm packing L41 

Flow rate: 1.0 mL/min 

Injection volume: 20 µL 

System suitability 

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

Suitability requirements 

Resolution: NLT 2.0 between levomedetomidine and dexmedetomidine, System suitability solution 

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

Relative standard deviation: NMT 3.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of levomedetomidine hydrochloride in the portion of sample taken: 

Result = (r_u/r_s) x (C_s/C_u) x 100 

r_u = peak height of levomedetomidine in the Sample solution 

r_s = peak height of levomedetomidine in the Standard solution 

C_s = concentration of USP Levomedetomidine RS in the Standard solution (µg/mL) 

C_u = concentration of Dexmedetomidine Hydrochloride in the Sample solution (µg/mL) 

Acceptance criteria: See Table 2. 

Table 2 

a (R)-4-[1-(2,3-Dimethylphenyl)ethyl]-1H-imidazole hydrochloride. 

5 SPECIFIC TESTS 

5.1 Loss on Drying 〈731〉 

Sample: 1.0 g 

Analysis: Dry the Sample at 105° for 3 h. 

Acceptance criteria: NMT 1.0% 

6 ADDITIONAL REQUIREMENTS 

6.1 Packaging and Storage: Store at controlled room temperature in tight containers in a dry place. 

6.2 USP Reference Standards 〈11〉 

USP Dexmedetomidine Hydrochloride RS 

USP Levomedetomidine RS 

(R)-4-[1-(2,3-Dimethylphenyl)ethyl]-1H-imidazole hydrochloride. 

C₁₃H₁₆N₂ . HCl           236.74