Gefitinib

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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C₂₂H₂₄CIFN₄O₃ 446.91

4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-;

N-(3-Chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine;

(3-Chloro-4-fluorophenyl)[7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-yl]amine CAS RN^®: 184475-35-2; UNII: S65743JHBS.

1 DEFINITION

Gefitinib contains NLT 98.0% and NMT 102.0% of gefitinib (C₂₂H₂₄CIFN₄O₃), calculated on the anhydrous basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197D

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: 9.7 g/L of ammonium acetate in water

Solution B: 0.2% trifluoroacetic acid in water

Mobile phase: Acetonitrile and Solution A (38:62)

Diluent: Acetonitrile and Solution B (40:60)

System suitability solution: 0.35 mg/mL of USP Gefitinib RS and 0.25 mg/mL of USP Dichloroaniline RS in Diluent. Sonicate to dissolve.

Standard solution: 0.35 mg/mL of USP Gefitinib RS in Diluent. Sonicate to dissolve.

Sample solution: 0.35 mg/mL of Gefitinib in Diluent. Sonicate to dissolve.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 247 nm

Column: 3.0-mm × 10-cm; 3-µm packing L1

Column temperature: 60°

Flow rate: 0.9 mL/min

Injection volume: 5 µL

Run time: NLT 5 times the retention time of gefitinib

3.3 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 5.0 between dichloroaniline and gefitinib, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of gefitinib (C₂₂H₂₄CIFN₄O₃) in the portion of Gefitinib taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of gefitinib from the Sample solution

r_S = peak response of gefitinib from the Standard solution

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

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

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.2%

4.2 ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution A: 0.7 µg/mL of USP Gefitinib RS in Diluent

Standard solution B: 0.7 µg/mL each of USP Gefitinib Related Compound A RS and USP Gefitinib Related Compound B RS in Diluent

Sensitivity solution: 0.18 µg/mL of USP Gefitinib RS from Standard solution A in Diluent

System suitability

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

[NOTE-The relative retention times in Table 1 are provided as information that could aid in peak assignment.]

Table 1

Suitability requirements

Resolution: NLT 5.0 between dichloroaniline and gefitinib, System suitability solution

Relative standard deviation: NMT 5.0% for gefitinib, Standard solution A; NMT 5.0% for gefitinib related compound A and gefitinib related compound B, Standard solution B

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

Analysis

Samples: Standard solution A, Standard solution B, and Sample solution

Calculate the percentage of gefitinib related compound A and gefitinib related compound B in the portion of Gefitinib taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of gefitinib related compound A or gefitinib related compound B from the Sample solution

r_S = peak response of gefitinib related compound A or gefitinib related compound B from Standard solution B

C_S = concentration of USP Gefitinib Related Compound A RS or USP Gefitinib Related Compound B RS in Standard solution B (mg/mL)

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

Calculate the percentage of any unspecified impurity in the portion of Gefitinib taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of any unspecified impurity from the Sample solution

r_S = peak response of gefitinib from Standard solution A

C_S = concentration of USP Gefitinib RS in Standard solution A (mg/mL)

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

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method I. Method la: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers and protect from light. Store at controlled room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Dichloroaniline RS

3,4-Dichloroaniline.

C₆H₅CI₂N 162.01

USP Gefitinib RS

USP Gefitinib Related Compound A RS

7-Methoxy-6-(3-morpholinopropoxy)quinazolin-4(3H)-one.

C₁₆H₂₁N₃O₄ 319.36

USP Gefitinib Related Compound B RS

N-(4-Chloro-3-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine.

C₂₂H₂₄CIFN₄O₃ 446.91(USP 1-Aug-2024)