Dried Plasma Spot (DPS) sampling in therapeutic drug monitoring (TDM) is a field of research in development. Compared with venous sampling, DPS sampling is a minimally invasive procedure where the patient’s finger is pricked and only a small volume of blood is sampled. Plasma concentration of sunitinib, a small molecule multi-targeted tyrosine kinase inhibitor, has proven the correlation with its efficacy and toxicity. TDM-guided dose adjustment of sunitinib could contribute to minimize the toxicity and to maximize the efficacy. This study describes the development of DPS assay for sunitinib and its metabolite, using high performance liquid chromatography tandem mass spectrometry.
Blood samplings of 4mL were performed 1-3 times from patients who were treated with sunitinib. DPS samples were prepared by applying 30 μL of spiked whole blood onto a Noviplex Card TM. Sunitinib and its metabolite were extracted with distilled water and methanol. The collected extract (3 μL) was injected onto a 100 mm × 2.1 mm 3μm Mastro TM C18 column and eluted with acetonitrile gradient into a triple quadrupole ESI-MS/MS Shimadzu LCMS-8050. Deming regression and Bland-Altman analyses were used to determine the relation between calculated and measured plasma concentrations. The study protocol was approved by our institutional review board and informed consent was obtained from all patients.
Four patients with thymic carcinoma were entered in this study. DPS concentrations and plasma concentrations of both sunitinib and its metabolite showed a strong correlation (r = 0.941 and 0.906, respectively). Subsequently, Bland-Altman analyses showed that 80% of sunitinib and 75% of its metabolite were within ± 20%, resulting in a high feasibility.
We have firstly developed a DPS assay of sunitinib and its metabolite, which is a convenient simple method. Our DPS assay showed comparable results to plasma samples, and could be applicable in routine clinical practice. For the application of DPS cards for TDM use, we are planning a validation study which patients use DPS cards themselves.
Clinical trial identification
Legal entity responsible for the study
Reiko Ando Makihara
Japan Research Foundation for Clinical Pharmacology
All authors have declared no conflicts of interest.