Levocetirizine Dihydrochloride Tablets

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

Levocetirizine Dihydrochloride Tablets contain NLT 90% and NMT 110% of the labeled amount of levocetirizine dihydrochloride (C₂₁H₂₅ClN₂O₃ ·2HCl).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U (CN 1-May-2020)

Medium: Water

Sample solution: Nominally 0.1 mg/mL of levocetirizine dihydrochloride from Tablets in water prepared as follows. Transfer 1 Tablet to a suitable volumetric flask, and add 40% of the flask volume of water. Shake for NLT 5 min to promote the disintegration of the Tablet. Dilute with water to volume. Pass a 10-mL portion of the resulting solution through a suitable filter, and discard the first mL. Use the filtrate.

Acceptance criteria: Meet the requirements

B. 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

3.1 Procedure

Solution A: 1 M sulfuric acid and water (5.7:94.3)

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

System suitability solution: 0.2 mg/mL of USP Levocetirizine Dihydrochloride RS and 0.2 μg/mL of USP Chlorobenzhydryl Piperazine RS in Mobile phase

Standard solution: 0.2 mg/mL of USP Levocetirizine Dihydrochloride RS in Mobile phase

Sample solution: Nominally 0.2 mg/mL of levocetirizine dihydrochloride prepared as follows. Transfer a number of Tablets (NLT 10), equivalent to 50 mg of levocetirizine dihydrochloride, to a 250-mL volumetric flask. Add 20 mL of Solution A, and put the flask on a mechanical shaker for 15 min. Add 150 mL of acetonitrile, and place the flask in an ultrasonic bath for 10 min. Allow the contents to cool to room temperature, if necessary, and dilute with acetonitrile to final volume. Homogenize the solution, and centrifuge a 10-mL portion for 5min. Use the supernatant solution.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Columns

Guard: 4-mm × 0.3-cm; 5-μm packing L3

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

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 μL

3.3 System suitability

Sample: System suitability solution

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

3.4 Suitability requirements

Resolution: NLT 3.0 between levocetirizine and chlorobenzhydryl piperazine

Tailing factor: NMT 1.5 for levocetirizine

Relative standard deviation: NMT 1.0% for levocetirizine

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of levocetirizine dihydrochloride (C₂₁H₂₅ClN₂O₃ · 2HCl) in the portion of Tablets taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of levocetirizine from the Sample solution

r_S = peak response of levocetirizine from the Standard solution

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

C_U = nominal concentration of levocetirizine dihydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90%–110%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: (L/900) mg/mL of USP Levocetirizine Dihydrochloride RS in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV-Vis

Analytical wavelength: 230 or 231 nm; use a suitable wavelength for background correction

Cell: 1 or 2 cm

Blank: Medium

Analysis

Samples: Standard solution,Sample solution, and Blank

Calculate the percentage of the labeled amount of levocetirizine dihydrochloride (C₂₁H₂₅ClN₂O₃ · 2HCl) dissolved:

Result = (A_U /A _S) × C_S × V × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of levocetirizine dihydrochloride (C₂₁H₂₅ClN₂O₃ · 2HCl) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Solution A, Mobile phase, System suitability solution, and Sample solution: Prepare as directed in the Assay.

Standard solution: 0.002 mg/mL of USP Levocetirizine Dihydrochloride RS in Mobile phase

Chromatographic system: Proceed as directed in the Assay, except for the Run time.

Run time: 2.3 times the retention time of levocetirizine

System suitability

Sample: System suitability solution

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

Suitability requirements

Resolution: NLT 3.0 between levocetirizine and chlorobenzhydryl piperazine

Tailing factor: NMT 1.5 for levocetirizine

Relative standard deviation: NMT 1.0% for levocetirizine; NMT 5.0% for chlorobenzhydryl piperazine

Analysis

Samples: Sample solution and Standard solution

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

Result = (r_U/r_S)x(C_S/C_U) × (M_r1 /M_r2 ) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of levocetirizine from the Standard solution

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

C_U = nominal concentration of levocetirizine dihydrochloride in the Sample solution (mg/mL)

M_r1 = molecular weight of levocetirizine (free base), 388.89

M_r2 = molecular weight of levocetirizine dihydrochloride, 461.81

Acceptance criteria: See Table 1. Disregard peaks less than 0.1%.

Table 1

^a This is a process impurity that is included in this table for identification only. This impurity is controlled in the drug substance. This impurity is not to be reported for the drug product and is not to be included in the total impurities.

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

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Chlorobenzhydryl Piperazine RS

(R)-1-[(4-Chlorophenyl)phenylmethyl]piperazine.

C₁₇H₁₉ClN₂ 286.80

USP Levocetirizine Dihydrochloride RS