Cetirizine 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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C₂₁H₂₅ClN₂O₃.2HCl 461.81 

(±)-[2-[4-[(4-Chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid, dihydrochloride; 

(±)-[2-[4-(p-Chloro-α-phenylbenzyl)-1-piperazinyl]ethoxy]acetic acid, dihydrochloride; 

(2-{4-[(4-Chlorophenyl)phenylmethyl]piperazin-1-yl}ethoxy)acetic acid dihydrochloride CAS RN®: 83881-52-1; UNII: 64O047KTOA. 

1 DEFINITION 

Cetirizine Hydrochloride contains NLT 98.0% and NMT 102.0% of cetirizine hydrochloride (C₂₁H₂₅ClN₂O₃.2HCl), calculated on the dried basis.  

2 IDENTIFICATION 

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

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

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

3 ASSAY 

Procedure 

Mobile phase: Acetonitrile, water, and 1 M sulfuric acid (93: 6.6: 0.4) 

Standard solution: 0.5 mg/mL of USP Cetirizine Hydrochloride RS in Mobile phase 

Sample solution: 0.5 mg/mL of Cetirizine Hydrochloride in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 230 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L3 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

Run time: NLT 3 times the retention time of the cetirizine peak 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 0.73% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of cetirizine hydrochloride (C₂₁H₂₅ClN₂O₃.2HCl) in the portion of Cetirizine Hydrochloride taken:  

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response cetirizine from the Sample solution 

r_S = peak response cetirizine from the Standard solution 

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

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

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

4 IMPURITIES 

Residue on Ignition 〈281〉 

Acceptance criteria: NMT 0.2% 

Organic Impurities, Procedure 1 

[Note—It is recommended that Organic Impurities, Procedure 2 be performed if either cetirizine Ethanol (2-{4-[(4-chloro phenyl)phenylmethyl]piperazin-1-yl}ethanol) or cetirizine acetic acid (2-{4-[(4-chloro phenyl)phenylmethyl]piperazin-1-yl}acetic acid) may be present in the test substance.] 

Mobile phase and Sample solution: Prepare as directed in the Assay. 

System suitability solution: 4 µg/mL each of USP Cetirizine Hydrochloride RS and USP Cetirizine Related Compound A RS in Mobile phase Sensitivity solution: 0.1 µg/mL of USP Cetirizine Hydrochloride RS in Mobile phase 

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

Chromatographic system: Proceed as directed in the Assay. 

System suitability 

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

[Note—See Table 1 for relative retention times.] 

Suitability requirements 

Resolution: NLT 2.0 between cetirizine and cetirizine related compound A, System suitability solution 

Tailing factor: NMT 2.0 for cetirizine, System suitability solution 

Relative standard deviation: NMT 2.0%, Standard solution 

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

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each individual specified or unspecified impurity in the portion of Cetirizine Hydrochloride taken: 

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

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

r_S = peak response of cetirizine from the Standard solution

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.02%. 

Table 1 

^a4-Chlorobenzhydrol.

^b 1,4-Bis[(4-chlorophenyl)phenylmethyl]piperazine. 

^c 2-(2-{4-[(2-Chlorophenyl)phenylmethyl]piperazin-1-yl}ethoxy)acetic acid. 

^d 2-{2-[4-(Diphenylmethyl)piperazin-1-yl]ethoxy}acetic acid. 

^e 1-[(4-Chlorophenyl)phenylmethyl]piperazine. 

Change to read: 

Organic Impurities, Procedure 2 

Solution A: 2 g/L of tetrabutylammonium hydrogen sulfate and 3 g/L of monobasic sodium phosphate monohydrate in water. Adjust with 1 N sodium hydroxide to a pH of 2.8 ± 0.05. 

Solution B: Methanol 

Buffer: 1.4 g/L of monobasic sodium phosphate monohydrate and 2.7 g/L of dibasic sodium phosphate heptahydrate. Adjust with either 1 N sodium hydroxide or 10% phosphoric acid to a pH of 6.9 ± 0.1. 

Mobile phase: See Table 2. 

Table 2 

Diluent: Acetonitrile and Buffer (50:50) 

Sensitivity solution: 1 µg/mL of USP Cetirizine Hydrochloride RS in Diluent 

Standard solution: 2 µg/mL of USP Cetirizine Hydrochloride RS in Diluent 

Sample solution: 2 mg/mL of Cetirizine Hydrochloride in Diluent 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 232 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L1 

Column temperature: 40° 

Flow rate: See Table 2. 

Injection volume: 10 µL 

System suitability 

Samples: Standard solution and Sensitivity solution 

[Note—See Table 3 for relative retention times.] 

Suitability requirements 

Column efficiency: NLT 6000 theoretical plates, Standard solution 

Relative standard deviation: NMT 5.0%, Standard solution 

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

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each individual specified or unspecified impurity in the portion of Cetirizine Hydrochloride taken:

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

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

r_S = peak response of cetirizine from the Standard solution

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

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

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.05%. 

Table 3 

^a 2-{2-[4-(Diphenylmethyl)piperazin-1-yl]ethoxy}acetic acid. 

^b 2-{4-[(4-Chlorophenyl)phenylmethyl]piperazin-1-yl}ethanol. 

^c 1-[(4-Chlorophenyl)phenylmethyl]piperazine. 

^d 2-(2-{4-[(2-Chlorophenyl)phenylmethyl]piperazin-1-yl}ethoxy)acetic acid. 

^e Methyl 2-(2-{4-[(4-chlorophenyl)phenylmethyl]piperazin-1-yl}ethoxy)acetate. 

^f 2-[2-[4-[(3-Chlorophenyl)phenylmethyl]piperazin-1-yl]ethoxy]acetic acid. 

^g 2-{4-[(4-Chlorophenyl)phenylmethyl]piperazin-1-yl}acetic acid. 

^h 2-(2-{4-[(4-Chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)acetic acid N1-oxide. 

ⁱ 4-Chlorobenzhydrol. 

^j (4-Chlorophenyl)phenylmethanone. 

^k 1,4-Bis[(4-chlorophenyl)phenylmethyl]piperazine. 

5 SPECIFIC TESTS 

pH 〈791〉 

Sample solution: 50 mg/mL in water 

Acceptance criteria: 1.2–1.8 

Loss on Drying 〈731〉 

Analysis: Dry at 105° to a constant weight. 

Acceptance criteria: NMT 0.5% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers, protected from light and moisture. Store at room temperature. Labeling: Label it to indicate with which impurity procedures the article complies. 

USP Reference Standards 〈11〉 

USP Cetirizine Hydrochloride RS 

USP Cetirizine Related Compound A RS 

(RS)-2-[2-[4-[(4-Chlorophenyl)phenylmethyl]piperazin-1-yl]ethoxy]acetic acid ethyl ester oxalate; also known as Ethyl 2-[2-{4-[(4-chlorophenyl) (phenyl)methyl]piperazin-1-yl}ethoxy]acetate oxalate salt. 

C₂₃H₂₉ClN₂O₃.C₂H₂O₄     506.97