Development of an LC-MS/MS Method for Measurement of Irinotecan and Its Major Metabolites in Plasma: Technical Considerations

Abstract Objective Irinotecan (CPT-11) is an important drug used in the treatment of several solid tumor types. To minimize its toxicity, therapeutic drug monitoring of CPT-11 and its major metabolites (SN-38, SN-38-glucuronide [SN-38G], and APC) has been proposed. We aimed to develop a liquid chrom...

Full description

Saved in:
Bibliographic Details
Published in:Laboratory medicine 2022-01, Vol.53 (1), p.47-52
Main Authors: Aoullay, Zineb, Van Wijk, Xander M R, Yanhui, Ma, Meddah, Bouchra, Lynch, Kara L, Cherrah, Yahia, Wu, Alan H B
Format: Article
Language:English
Subjects:
Analysis
Antineoplastic Agents, Phytogenic
Chromatography, High Pressure Liquid
Chromatography, Liquid
Ethylenediaminetetraacetic acid
Health aspects
Humans
Ionization
Ions
Irinotecan
Liquid chromatography
Mass spectrometry
Measurement
Metabolites
Methods
Pharmaceutical Preparations
Reproducibility of Results
Tandem Mass Spectrometry
Therapeutic drug monitoring
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Objective Irinotecan (CPT-11) is an important drug used in the treatment of several solid tumor types. To minimize its toxicity, therapeutic drug monitoring of CPT-11 and its major metabolites (SN-38, SN-38-glucuronide [SN-38G], and APC) has been proposed. We aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of CPT-11 and its major metabolites in plasma. Methods Specimen preparation consisted of protein precipitation, evaporation, and reconstitution. Analyses were performed on a C18 column using reverse-phase gradient elution. Electrospray ionization and multiple reaction monitoring in positive mode were used for MS. The following heavy isotope–labeled internal standards were used: CPT-11 D10, SN-38 D3, SN-38G D3, and APC D3. Results We found that CPT-11, SN-38G, and APC eluted at ~4.6 to 4.7 minutes, and SN-38 eluted at ~5.1 to 5.2 minutes. A second peak for SN-38 was detected at ~4.6 to 4.7 minutes. Given that the structure of SN-38 is found in CPT-11, SN-38G, and APC, and in the CPT-11 D10 used here, in-source fragmentation was the likely cause. In addition, we found that a low-level SN-38 impurity was present in CPT-11 D10 and to a lesser extent in SN-38 D3. Conclusion When developing methods for CPT-11 and its metabolites, it is important to consider the effects of in-source fragmentation and the choice of internal standards.
ISSN:0007-5027
1943-7730
DOI:10.1093/labmed/lmab059