Irinotecan Hydrochloride Injection

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 

Irinotecan Hydrochloride Injection is a sterile solution of Irinotecan Hydrochloride in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of irinotecan hydrochloride (C₃₃H₃₈N₄O₆.HCl · 3H₂O). 

2 IDENTIFICATION 

Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U 

Sample solution: 4 µg/mL 

Medium: Methanol 

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 

Buffer: Dissolve 2 g of sodium 1-hexanesulfonate and 2 mL of triethylamine in 1 L of water. 

Mobile phase: Acetonitrile and Buffer (34:66). Adjust with phosphoric acid to a pH of 2.5. 

Standard solution: 0.04 mg/mL of USP Irinotecan Hydrochloride RS in Mobile phase. Sonication and shaking may be used to aid dissolution. Sample solution: 0.04 mg/mL of irinotecan hydrochloride in Mobile phase from Injection 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L7 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.5 

Relative standard deviation: NMT 1.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of irinotecan hydrochloride (C₃₃H₃₈N₄O₆.HCl .3H₂O) in the portion of Injection taken: 

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

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

C_S = concentration of USP Irinotecan Hydrochloride RS in the Standard solution (µg/mL) 

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

M_r1 = molecular weight of irinotecan hydrochloride (C₃₃H₃₈N₄O₆.HCl. 3H₂O), 677.18

M_r2 = molecular weight of irinotecan hydrochloride, anhydrous (C₃₃H₃₈N₄O₆.HCl), 623.14

Acceptance criteria: 90.0%–110.0% 

4 IMPURITIES 

Organic Impurities 

Solution A: Dissolve 2 g of sodium 1-hexanesulfonate and 1 mL of triethylamine in 1 L of water. Adjust with phosphoric acid to a pH of 2.5. 

Solution B: Acetonitrile 

Mobile phase: See Table 1. 

Table 1 

Diluent: Acetonitrile, phosphoric acid, and Solution A (500:15:500) 

System suitability solution: 0.2 mg/mL of USP Irinotecan Hydrochloride RS and 0.4 µg/mL of irinotecan related compound E in Diluent, added stepwise, if necessary. Sonication may be used to aid dissolution. 

Sample solution: 0.2 mg/mL of irinotecan hydrochloride in Diluent from Injection 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

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

Flow rate: 1 mL/min 

Temperatures 

Column: 55° 

Sample: 15° 

Injection volume: 25 µL 

System suitability 

Sample: System suitability solution 

Suitability requirements 

Resolution: NLT 4.0 between irinotecan and irinotecan related compound E 

Analysis 

Sample: Sample solution 

Calculate the percentage of each impurity in the portion of Irinotecan Hydrochloride Injection taken: 

Result = (r_U/r_T) × (1/F) × 100 

r_U = peak area of each impurity from the Sample solution 

r_T = sum of the peak areas from the Sample solution 

F = relative response factor for each individual impurity (see Table 2) 

Acceptance criteria: See Table 2. 

Table 2 

^a(S)-4,11-Diethyl-4,9-dihydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione.

^b(S)-4-Ethyl-4-hydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione. It is a process impurity and is controlled in the API monograph. 

^cIrinotecan related compound E. It is a process impurity and is controlled in the API monograph. 

^d These process impurities are included in the table for identification only and are not included in the Total impurities. 

5 SPECIFIC TESTS 

Bacterial Endotoxins Test 〈85〉: NMT 0.83 USP Endotoxin Units/mg of irinotecan hydrochloride 

Sterility Tests 〈71〉: Meets the requirements when tested as directed for Test for Sterility of the Product to Be Examined, Membrane Filtration pH 〈791〉: 3.0–3.8 

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections 

Other Requirements: Meets the requirements under Injections and Implanted Drug Products 〈1〉 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in single-dose vials, protected from light. Store at controlled room temperature. 

Labeling: Label it to indicate that it is to be diluted with either 5% dextrose solution (USP) or 0.9% Sodium Chloride Injection (USP) prior to intravenous infusion. 

USP Reference Standards 〈11〉 

USP Irinotecan Hydrochloride RS 

USP Irinotecan Related Compound E RS 

(S)-4,11-Diethyl-4-hydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione. 

C₂₂H₂₀N₂O₄ 376.41