Cetirizine Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release 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 

Cetirizine Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of cetirizine hydrochloride (C₂₁H₂₅ClN₂O₃.2HCl) and pseudoephedrine hydrochloride (C₁₀H₁₅NO.HCl). 

2 IDENTIFICATION 

A. The retention times of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay. 

3 ASSAY 

Cetirizine Hydrochloride 

Buffer: 3.5 g/L of monobasic ammonium phosphate and 1.0 g/L of tetrabutylammonium bisulfate in water. Adjust with phosphoric acid to a pH of 2.5. 

Diluent: Methanol and Buffer (2:3) 

Solution A: Acetonitrile, methanol, and Buffer (9:2:29) Solution B: Acetonitrile 

Mobile phase: See Table 1. 

Table 1

Standard stock solution: 0.5 mg/mL of USP Cetirizine Hydrochloride RS in Diluent. [Note—Sonicate to dissolve.] Standard solution: 0.025 mg/mL of USP Cetirizine Hydrochloride RS in Diluent from the Standard stock solution Sample solution: 0.025 mg/mL of cetirizine hydrochloride (from NMT 10 finely powdered Tablets) prepared as follows. Dissolve the Tablets first in methanol, using 22.5% of the nal flask volume. Sonicate for NLT 20 min with vigorous swirling every 5 min. To the solution add a volume of Buffer equal to 26% of the nal flask volume. Allow the solution to equilibrate to room temperature. Dilute with Diluent to volume. Pass a portion through a membrane filter of 0.45-µm pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 230 nm 

Column: 4.6-mm × 15-cm; 3.5-µm packing L1 

Temperatures 

Column: 30° 

Autosampler: 5° 

Flow rate: 1 mL/min 

Injection volume: 25 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tablets Column efficiency: NLT 3000 theoretical plates 

Tailing factor: NMT 1.5 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

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

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of cetirizine 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 = nominal concentration of cetirizine hydrochloride in the Sample solution (mg/mL) 

Acceptance criteria: 90.0%–110.0% 

Pseudoephedrine Hydrochloride 

Buffer: 0.8 g/L of ammonium acetate in water. To 1 L of the solution add 1.0 mL of triethylamine. Adjust with glacial acetic acid to a pH of 4.5. 

Mobile phase: Acetonitrile and Buffer (3:7) 

Standard solution: 0.5 mg/mL of USP Pseudoephedrine Hydrochloride RS in Mobile phase. [Note—Sonicate to dissolve.] Sample stock solution: 2.4 mg/mL of pseudoephedrine hydrochloride (from 5 finely powdered Tablets) prepared as follows. Dissolve the crushed Tablets first in acetonitrile, using 24% of the nal flask volume. Sonicate for NLT 15 min. To the solution add a volume of Buffer 

equal to 56% of the nal flask volume. Sonicate for NLT 15 min. Shake the flask for NLT 10 min. Allow the solution to equilibrate to room temperature. Dilute with Mobile phase to volume. Centrifuge a portion for 15 min to obtain a clear supernatant. 

Sample solution: 0.5 mg/mL of pseudoephedrine hydrochloride in Mobile phase from the Sample stock solution. Pass the solution through a membrane filter of 0.45-µm pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L9 

Flow rate: 1.5 mL/min 

Injection volume: 25 µL 

Run time: 2 times the retention time of pseudoephedrine 

System suitability 

Sample: Standard solution 

Suitability requirements 

Column efficiency: NLT 1000 theoretical plates 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of pseudoephedrine hydrochloride (C₁₀H₁₅NO.HCl) in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of pseudoephedrine from the Sample solution 

r_S = peak response of pseudoephedrine from the Standard solution 

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

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

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS 

Dissolution 〈711〉 

Test 1 

Medium: 0.1 N hydrochloric acid; 500 mL, deaerated 

Apparatus 1: 100 rpm 

Time: 30 min for cetirizine hydrochloride and 30 min (used only for adjustments in the calculations); 1, 2, and 6 h for pseudoephedrine hydrochloride 

Buffer: 0.77 g/L of ammonium acetate in water. To 1 L of the solution add 1.0 mL of triethylamine. Adjust with glacial acetic acid to a pH of 4.5 ± 0.05. 

Mobile phase: Acetonitrile and Buffer (3:7) 

Standard stock solution: 0.5 mg/mL of USP Cetirizine Hydrochloride RS in water 

Standard solution: 0.24 mg/mL of USP Pseudoephedrine Hydrochloride RS and 0.01 mg/mL of USP Cetirizine Hydrochloride RS in Medium from the Standard stock solution 

Sample solution: At the times specified, withdraw 5 mL of the solution under test, and pass through a suitable filter of 0.45-µm pore size, discarding the first few mL. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV, 230 nm for cetirizine hydrochloride, 254 nm for pseudoephedrine hydrochloride 

Column: 4.6-mm × 15-cm; 5-µm packing L9 

Flow rate: 1.5 mL/min 

Injection volume: 25 µL 

Run time: 2 times the retention time of pseudoephedrine 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0 for both cetirizine and pseudoephedrine 

Relative standard deviation: NMT 2.0% for both cetirizine and pseudoephedrine 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of cetirizine hydrochloride dissolved: 

Result = (r_U/r_S) × (C_S/L) × V × 100 

r_U = peak response of cetirizine from the Sample solution 

r_S = peak response of cetirizine from the Standard solution 

C_S = concentration of cetirizine hydrochloride in the Standard solution (mg/mL) 

L = label claim for cetirizine hydrochloride (mg/Tablet) 

V = volume of Medium, 500 mL 

Calculate the percentage of pseudoephedrine hydrochloride dissolved at each time point: 

Q₃₀= (r_U/r_S) × (C_S/L) × V × 100 

Q₁ = (Q₃₀ × 5/500) + [(r_U/r_S) × (C_S/L) × 495 × 100] 

Q₂ = (Q₃₀ × 5/500) + (Q₁ × 5/495) + [(r_U/r_S) × (C_S/L) × 490 × 100] 

Q₆ = (Q₃₀ × 5/500) + (Q₁ × 5/495) + (Q₂ × 5/490) + [(r_U/r_S) × (C_S/L) × 485 × 100] 

r_U = peak response of pseudoephedrine from the Sample solution 

r_S = peak response of pseudoephedrine from the Standard solution 

C_S = concentration of pseudoephedrine hydrochloride in the Standard solution (mg/mL) 

L = label claim for pseudoephedrine hydrochloride (mg/Tablet) 

V = initial volume of Medium, 500 mL 

Tolerances 

Cetirizine hydrochloride: NLT 80% (Q) of the labeled amount of cetirizine hydrochloride is dissolved in 30 min. Pseudoephedrine hydrochloride (C₁₀H₁₅NO.HCl): See Table 2. 

Table 2 

The percentages of the labeled amount of pseudoephedrine hydrochloride dissolved at the times specied conform to Acceptance Table 2 in 〈711〉. 

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. 

Medium: 0.1 N HCl; 500 mL 

Apparatus 1: 100 rpm 

Time: 30 min for cetirizine hydrochloride and 30 min (used only for adjustments in the calculations); 1, 2, 4 and 8 h for pseudoephedrine hydrochloride 

Buffer: 6.8 g/L of sodium acetate and 16.2 g/L of sodium 1-octanesulfonate 

Mobile phase: Methanol and Buffer (50:50). Adjust with glacial acetic acid to a pH of 5.5. 

Standard solution: 0.01 mg/mL of USP Cetirizine Hydrochloride RS and 0.24 mg/mL of USP Pseudoephedrine Hydrochloride RS in Medium Sample solution: Pass a 5-mL portion of the solution under test through a suitable filter of 0.45-µm pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 242 nm 

Column: 4.6-mm × 10-cm; 5-µm packing L1 

Column temperature: 35° 

Flow rate: 2 mL/min 

Injection volume: 100 µL 

System suitability 

[Note—The relative retention times for pseudoephedrine and cetirizine are 1.0 and 2.9, respectively.] 

Sample: Standard solution 

Suitability requirements 

Column efficiency: NLT 2000 theoretical plates for both pseudoephedrine and cetirizine 

Tailing factor: NMT 2.0 for both pseudoephedrine and cetirizine 

Relative standard deviation: NMT 2.0% for both pseudoephedrine and cetirizine 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of cetirizine hydrochloride (C₂₁H₂₅ClN₂O₃.2HCl) dissolved:

Result = (r_U/r_S) × (C_S/L) × V × 100 

r_U = peak response of cetirizine 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) 

L = label claim (mg/Tablet) 

V = volume of Medium, 500 mL 

Calculate the concentration (C ) of pseudoephedrine hydrochloride (C₁₀H₁₅NO.HCl) in the sample withdrawn from the vessel at each time point (i) shown in Table 3: 

Result = r_U/r_S) × C_S

r_U = peak response of pseudoephedrine from the Sample solution 

r_S = peak response of pseudoephedrine from the Standard solution 

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

Calculate the percentage of the labeled amounts (Q) of pseudoephedrine hydrochloride (C₂₁H₂₅ClN₂O₃.2HCl) dissolved at each time point (i) shown in Table 3: 

Result₁ = C₁ × V × (1/L) × 100 

Result₂ = {[C₂ × (V − V_s )] + (C₁ × V_s)} × (1/L) × 100 

Result₃ = {[C₃ × [V − (2 × V_s )]] + [(C₂ + C₁ ) × V_s ]} × (1/L) × 100 

Result₄ = {[C₄ × [V − (3 × V_s )]] + [(C₃ + C₂ + C₁ ) × V_s ]} × (1/L) × 100 

Result₅ = {[C₅ × [V − (4 × V_s )]] + [(C₄ + C₃ + C₂ + C₁ ) × V_s ]} × (1/L) × 100 

C₁= concentration of pseudoephedrine hydrochloride in the portion of sample withdrawn at time point (i) (mg/mL) 

V = volume of the Medium (500 mL) 

V_s = volume of the Sample solution withdrawn from the Medium (mL) 

L = label claim for pseudoephedrine hydrochloride (mg/Tablet) 

Tolerances 

Cetirizine hydrochloride: NLT 75% (Q) of the labeled amount of cetirizine hydrochloride (C₂₁H₂₅ClN₂O₃.2HCl) is dissolved. Pseudoephedrine hydrochloride (C₁₀H₁₅NO.HCl): See Table 3. 

Table 3 

The percentages of the labeled amount of pseudoephedrine hydrochloride dissolved at the times specied conform to Acceptance Table 2 in 〈711〉. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Cetirizine Hydrochloride Related Compounds 

Buffer, Diluent, Solution A, and Solution B: Proceed as directed in the Assay for Cetirizine hydrochloride. 

Mobile phase: See Table 4. 

Table 4 

Standard stock solution: 0.5 mg/mL of USP Cetirizine Hydrochloride RS in Diluent. [Note—Sonicate to dissolve.] 

Standard solution: 1 µg/mL of USP Cetirizine Hydrochloride RS in Diluent from the Standard stock solution 

Sample stock solution: 0.5 mg/mL of cetirizine hydrochloride (from NMT 10 finely powdered Tablets) prepared as follows. Dissolve the Tablets first in methanol, using 70% of the final flask volume. Sonicate for 15 min, and then shake for 15 min. Allow the solution to cool to room temperature, and dilute with methanol to volume. Centrifuge a portion for 10 min. 

Sample solution: 0.2 mg/mL of cetirizine hydrochloride in Buffer from the Sample stock solution. Pass a portion through a suitable membrane filter of 0.45-µm pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 230 nm 

Column: 4.6-mm × 15-cm; 3.5-µm packing L1 

Temperatures 

Column: 30° 

Autosampler: 5° 

Flow rate: 1 mL/min 

Injection volume: 25 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Column efficiency: NLT 1300 theoretical plates 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 5.0% 

Analysis 

Samples: Standard solution and Sample solution 

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

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

r_U = peak response of the individual 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 = nominal concentration of cetirizine hydrochloride in the Sample solution (mg/mL) 

F = relative response factor (see Table 5) 

Acceptance criteria: See Table 5. 

[Note—Disregard any peak less than 0.05% of the main peak.] 

Table 5 

^_a 2-[4-[(4-Chlorophenyl)phenylmethyl]piperazin-1-yl]ethanol. 

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

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

^d 2-[4-[(4-Chlorophenyl)phenylmethyl]-1-oxide-1-piperazinyl]ethoxy]acetic acid. 

Pseudoephedrine Hydrochloride Related Compounds 

Buffer: 11.2 g/L of sodium perchlorate monohydrate in water. Adjust with hydrochloric acid to a pH of 2.7. 

Solution A: Methanol and Buffer (3:17) 

Solution B: Methanol and Buffer (1:1) 

Diluent: Solution A 

Mobile phase: See Table 6. 

Table 6 

Standard stock solution: 0.48 mg/mL of USP Pseudoephedrine Hydrochloride RS in Diluent 

Standard solution: 4.8 µg/mL of USP Pseudoephedrine Hydrochloride RS in Diluent from the Standard stock solution System suitability stock solution: 49 µg/mL of ephedrine in Diluent from USP Ephedrine Sulfate RS 

System suitability solution: 1.96 µg/mL of ephedrine and 0.46 mg/mL of USP Pseudoephedrine Hydrochloride RS in Standard stock solution from the System suitability stock solution and the Standard stock solution, respectively 

Sample stock solution: 2.4 mg/mL of pseudoephedrine hydrochloride (from NMT 25 finely powdered Tablets) prepared as follows. Dissolve the Tablets first in methanol, using 75% of the nal flask volume. Sonicate for NLT 15 min, and then shake for 15 min. Allow the solution to cool to room temperature, and dilute with methanol to volume. Centrifuge a portion for 10 min. 

Sample solution: 0.48 mg/mL of pseudoephedrine hydrochloride in Diluent from the Sample stock solution. Pass a portion through a suitable membrane filter of 0.45-µm pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 212 nm 

Column: 4.6-mm × 25-cm; 4-µm packing L11 

Column temperature: 40° 

Flow rate: 1 mL/min 

Injection volume: 30 µL 

System suitability 

Samples: Standard solution and System suitability solution 

Suitability requirements 

Resolution: NLT 1.3 between ephedrine and pseudoephedrine, System suitability solution 

Tailing factor: NMT 1.5, Standard solution 

Relative standard deviation: NMT 3.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

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

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

r_U = peak response of the individual impurity from the Sample solution 

r_S = peak response of pseudoephedrine from the Standard solution 

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

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

F = relative response factor (see Table 7) 

Acceptance criteria: See Table 7. 

[Note—Disregard any peak less than 0.05% of the main peak.] 

Table 7 

^a[R-(R*,S*)]-α-[1-(Methylamino)ethyl]-benzenemethanol.

^b For system suitability and identification purposes only. 

^c 2-Methylamino-1-phenylpropan-1-one. 

Sum of cetirizine and pseudoephedrine related impurities: NMT 1.0% 

6 ADDITIONAL REQUIREMENTS 

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

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used. 

USP Reference Standards 〈11〉 

USP Cetirizine Hydrochloride RS 

USP Ephedrine Sulfate RS 

USP Pseudoephedrine Hydrochloride RS