Cetirizine Hydrochloride Oral Solution
DEFINITION
Cetirizine Hydrochloride Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of C21H25ClN2O3·2HCl.
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. Identification Tests—General, Chloride 191: Meets the requirements
ASSAY
•  Procedure
Solution A:  Acetonitrile
Solution B:  1.36 g/L of monobasic potassium phosphate in water. Adjust with a 2% solution of phosphoric acid in water to a pH of 3.5 ± 0.05.
Diluent:  Acetonitrile and water (3:7)
Mobile phase:  See the gradient table below.
Time
(min)
Solution A
(%)
Solution B
(%)
0 5 95
15 5 95
22 25 75
35 25 75
40 5 95
50 5 95
Standard stock solution:  5 mg/mL of USP Cetirizine Hydrochloride RS in water
Standard solution:  0.1 mg/mL of USP Cetirizine Hydrochloride RS in Diluent, from the Standard stock solution
Sample solution:  Transfer an amount of Oral Solution to a suitable volumetric flask to obtain a nominal concentration of 0.1 mg/mL of cetirizine hydrochloride. Dissolve in 60% of the flask volume of Diluent by swirling. Sonicate 3 min, and dilute with Diluent to volume. Pass through a suitable filter.
Chromatographic system 
Mode:  LC
Detector:  UV 233 nm
Column:  4.6-mm × 25-cm; 5-µm packing L10
Column temperature:  50
Flow rate:  2 mL/min
Injection size:  20 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Tailing factor:  NMT 1.5
Relative standard deviation:  NMT 1.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C21H25ClN2O3 ·2HCl in the portion of Oral Solution taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of USP Cetirizine Hydrochloride RS in the Standard solution (mg/mL)
CU== nominal concentration of cetirizine hydrochloride in the Sample solution (mg/mL)
Acceptance criteria:  90.0%–110.0%
PERFORMANCE TESTS
•  Deliverable Volume 698: Meets the requirements
IMPURITIES
Organic Impurities 
•  Procedure
Solution A:  Transfer 50 mL of water to a 100-mL volumetric flask, add 5.5 mL of sulfuric acid, and dilute with water to volume.
Mobile phase:  Acetonitrile, water, and Solution A (965:33:1)
Diluent:  Acetonitrile and water (7:13)
Standard solution:  6 µg/mL of USP Cetirizine Hydrochloride RS in Diluent
Sample solution:  0.6 mg/mL of cetirizine hydrochloride in Diluent. Transfer an amount of Oral Solution to a suitable volumetric flask, dissolve in Diluent, sonicate for 10 min, and dilute with Diluent to volume. Pass through a suitable filter.
Chromatographic system  
Mode:  LC
Detector:  UV 230 nm
Column:  4.6-mm × 25-cm; 5-µm packing L3
Column temperature:  30
Flow rate:  2 mL/min
Injection size:  10 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Column efficiency:  NLT 10,000 theoretical plates
Tailing factor:  NMT 1.5
Relative standard deviation:  NMT 5.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Oral Solution taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response for each impurity from the Sample solution
rS== peak response for cetirizine from the Standard solution
CS== concentration of USP Cetirizine Hydrochloride RS in the Standard solution (mg/mL)
CU== nominal concentration of cetirizine hydrochloride in the Sample solution (mg/mL)
Acceptance criteria:  See Impurity Table 1.
Total impurities:  NMT 0.8%
Impurity Table 1
Name Relative
Retention
Time
Acceptance Criteria,
NMT (%)
Cetirizine acetic acida 0.69 Pb
2-Chlorocetirizinec 0.83 P
Cetirizine 1.00
Cetirizineethanold 1.30 P
Ethoxycetirizinee 1.38 P
CBHPf 1.52 P
Propylene glycol ester of cetirizine (diastereomer 1)g 1.53 0.2
Propylene glycol ester of cetirizine (diastereomer 2)g 1.61 0.2
Deschlorocetirizineh 1.65 P
Glyceryl ester of cetirizinei 2.20 0.5
Any individual unspecified impurity 0.2
a  2-[4-[(4-Chlorophenyl)phenylmethyl]piperazin-1-yl]acetic acid.
b  P = Process impurity. Provided for information only; the content is not calculated and not reported. The content is controlled in the drug substance monograph.
c  2-[2-[4-[(2-Chlorophenyl)phenylmethyl]piperazin-1-yl]ethoxy]acetic acid.
d  2-[4-[(4-Chlorophenyl)phenylmethyl]piperazin-1-yl]ethanol.
e  2-[2-[2-[4-[(4-Chlorophenyl)phenylmethyl]piperazin-1-yl]ethoxy] ethoxy]acetic acid (ethoxycetirizine).
f  1-[(4-Chlorophenyl)phenylmethyl]piperazine.
g  2-Hydroxypropyl 2-(2-{4-[(4-chlorophenyl)phenylmethyl]piperazin-1-yl}ethoxy)acetate.
h  2-{2-[4-(Diphenylmethyl)piperazin-1-yl]ethoxy]acetic acid.
i  2,3-Dihydroxypropyl 2-(2-{4-[(4-chlorophenyl)phenylmethyl]piperazin-1-yl}ethoxy)acetate.
SPECIFIC TESTS
•  pH 791: 4.0–5.1
•  Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62: The total aerobic microbial count does not exceed 100 cfu/mL, and the total combined molds and yeasts count does not exceed 10 cfu/mL. It meets the requirements of the tests for absence of Escherichia coli.
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in well-closed containers, and protect from light. Store at controlled room temperature or in a cold place.
•   USP Reference Standards 11
USP Cetirizine Hydrochloride RS Click to View Structure
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Domenick Vicchio, Ph.D.
Senior Scientific Liaison
1-301-998-6828
(SM42010) Monographs - Small Molecules 4
61 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
1-301-816-8339
(GCM2010) General Chapters - Microbiology
62 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
1-301-816-8339
(GCM2010) General Chapters - Microbiology
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 2598