Irinotecan Lactone Impurity

• CAT Number: R051686
• CAS Number: 143490-53-3
• Molecular Formula: C32H36N4O5
• Molecular Weight: 556.663
• Purity: ≥95%
• Synonyms: [1,4’-Bipiperidine]-1’-carboxylic Acid 3,10-Diethyl-11,13-dihydro-1,13-dioxo-1H,3H- furo[3’,4’:6,7]indolizino[1,2-b]quinolin-8-yl Ester
• Storage: -20°C
• InChI: InChI=1S/C32H36N4O5/c1-3-21-22-16-20(40-32(39)35-14-10-19(11-15-35)34-12-6-5-7-13-34)8-9-25(22)33-29-24(21)18-36-26(29)17-23-27(4-2)41-31(38)28(23)30(36)37/h8-9,16-17,19,27H,3-7,10-15,18H2,1-2H3
• InChIKey: MPKLBQKGQFVIOG-UHFFFAOYSA-N
• SMILES: CCC1C2=C(C(=O)N3CC4=C(C3=C2)N=C5C=CC(=CC5=C4CC)OC(=O)N6CCC(CC6)N7CCCCC7)C(=O)O1

Irinotecan Lactone Impurity(CAS: 143490-53-3) is a lactone impurity of Irinotecan (I767500), a DNA topoisomerase inhibitor. A photodegradation product of a camptothecin derivative used as an anticancer drug.

Reference

[1]. J Chromatogr Sci. 2012 Oct;50(9):810-9. doi: 10.1093/chromsci/bms075. Epub 2012 Jun 1.
UPLC and LC-MS studies on degradation behavior of irinotecan hydrochloride and development of a validated stability-indicating ultra-performance liquid chromatographic method for determination of irinotecan hydrochloride and its impurities in pharmaceutical dosage forms.
Kumar N(1), Sangeetha D, Reddy SP.
Author information: (1)Dr. Reddy's Laboratories Ltd., IPDO, Bachupally, Hyderabad-500072, A.P, India.
The objective of the current investigation was to study the degradation behavior of irinotecan hydrochloride under different International Conference on Harmonization (ICH) recommended stress conditions using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry and to establish a validated stability-indicating reverse-phase ultra-performance liquid chromatographic method for the quantitative determination of irinotecan hydrochloride and its seven impurities and degradation products in pharmaceutical dosage forms. Irinotecan hydrochloride was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Irinotecan hydrochloride was found to degrade significantly in oxidative and base hydrolysis and photolytic degradation conditions. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. Chromatographic separation was achieved on a Waters Acquity BEH C8 (100 × 2.1 mm) 1.7-µm column with a mobile phase containing a gradient mixture of solvent A (0.02M KH(2)PO(4) buffer, pH 3.4) and solvent B (a mixture of acetonitrile and methanol in the ratio of 62:38 v/v). The mobile phase was delivered at a flow rate of 0.3 mL/min with ultraviolet detection at 220 nm. The run time was 8 min, within which irinotecan and its seven impurities and degradation products were satisfactorily separated. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of irinotecan hydrochloride in pharmaceutical dosage forms.
DOI: 10.1093/chromsci/bms075 PMID: 22661461 [Indexed for MEDLINE]

[2]. Biomacromolecules. 2017 Jun 12;18(6):1874-1884. doi: 10.1021/acs.biomac.7b00317. Epub 2017 May 11.
Synthesis and Characterization of Micelle-Forming PEG-Poly(Amino Acid) Copolymers with Iron-Hydroxamate Cross-Linkable Blocks for Encapsulation and Release of Hydrophobic Drugs.
Sill KN(1), Sullivan B(1), Carie A(1), Semple JE(1).
Author information: (1)Intezyne Technologies , 3720 Spectrum Boulevard, Suite 104, Tampa, Florida 33612, United States.
Described is the development of a polymeric micelle drug delivery platform that addresses the physical property limitations of many nanovectors. The system employs triblock copolymers comprised of a hydrophilic poly(ethylene glycol) (PEG) block, and two poly(amino acid) (PAA) blocks: a stabilizing cross-linking central block, and a hydrophobic drug encapsulation block. Detailed description of synthetic strategies and considerations found to be critical are discussed. Of note, it was determined that the purity of the α-amino acid-N-carboxyanhydrides (NCA) monomers and PEG macroinitiator are ultimately responsible for impurities that arise during the polymerization. Also, contrary to current beliefs in the field, the presence of water does not adversely affect the polymerization of NCAs. Furthermore, we describe the impact of poly(amino acid) conformational changes, through the incorporation of d-amino acids to form mixed stereochemistry PAA blocks, with regard to the physical and pharmacokinetic properties of the resulting micelles.
DOI: 10.1021/acs.biomac.7b00317 PMID: 28475303 [Indexed for MEDLINE]

[3]. Simultaneous determination of a camptothecin derivative, used as an anticancer drug, and its photodegradation products by high-performance liquid chromatography
Katsuya Akimoto, Akiko Kawai, Kazumi Ohya,
Journal of Chromatography A, Volume 734, Issue 2, 1996, Pages 401-404, ISSN 0021-9673, https://doi.org/10.1016/0021-9673(96)00013-1. (https://www.sciencedirect.com/science/article/pii/0021967396000131)
Abstract: A simple and rapid ion-pair high-performance liquid chromatographic method using a polymer-based column bonded octadecyl group was developed for the simultaneous determination of the anticancer drug CPT-11 and its three main photodegradation products. The analytes were detected by ultraviolet absorption at 254 nm.