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Development of an LC-MS/MS Method for Measurement of Irinotecan and Its Major Metabolites in Plasma: Technical Considerations
- Source :
- Laboratory Medicine. 53:47-52
- Publication Year :
- 2021
- Publisher :
- Oxford University Press (OUP), 2021.
-
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.
- Subjects :
- Chromatography
medicine.diagnostic_test
Chemistry
Elution
Electrospray ionization
Biochemistry (medical)
Clinical Biochemistry
Selected reaction monitoring
Reproducibility of Results
Irinotecan
Mass spectrometry
Antineoplastic Agents, Phytogenic
Pharmaceutical Preparations
Tandem Mass Spectrometry
Therapeutic drug monitoring
medicine
Humans
Protein precipitation
Fragmentation (cell biology)
Chromatography, High Pressure Liquid
Chromatography, Liquid
medicine.drug
Subjects
Details
- ISSN :
- 19437730 and 00075027
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Laboratory Medicine
- Accession number :
- edsair.doi.dedup.....481b8643535489bf312f1da30fdb0d10