A New High-Performance Liquid Chromatography–Tandem Mass Spectrometry Method for the Determination of Sunitinib and N-desethyl sunitinib in Human Plasma: Light-Induced Isomerism Overtaking Towards Therapeutic Drug Monitoring in Clinical Routine

Publication date: Available online 25 October 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Elena Marangon, Mauro Buzzo, Bianca Posocco, Sara Gagno, Martina Zanchetta, Valentina Iacuzzi, Ariana Soledad Poetto, Michela Guardascione, Luciana Giodini, Giuseppe ToffoliAbstractSunitinib is approved for advanced renal cell cancer, imatinib-resistant or -intolerant gastrointestinal stromal tumors and pancreatic neuroendocrine cancers. It is prescribed at a fixed dose but its plasma exposure shows large inter-individual variations. Taking into account the narrow therapeutic window and the positive exposure-efficacy relationship, there is a robust rationale for its therapeutic drug monitoring. In fact, a target plasma concentration of sunitinib plus its active metabolite, N-desethyl sunitinib, ≥50 ng/mL was suggested. In order to quantify sunitinib and N-desethyl sunitinib in patients’ plasma, we developed and validated a new LC-MS/MS method applicable to clinical routine. In solution, sunitinib and N-desethyl sunitinib undergo to photo-isomerization and many published methods overcome this problem by conducting the entire procedures of samples collection and handling under strictly light-protection. Our method is based on a simple and fast procedure that quantitatively reconverts the E-isomer of both analytes, obtained during sample draw and processing without light-protection, into their Z-forms. Moreover, our method uses a small plasma volume (30 Â...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research