pH-Mediated molecular differentiation for fluorimetric quantification of chemotherapeutic drugs in human plasma

Luis A. Serrano, Ye Yang, Elisa Salvati, Francesco Stellacci, Silke Krol and Stefan Guldin

At present, drug dosage is based on standardised approaches that disregard pharmakokinetic differences between patients and lead to non-optimal efficacy and unnecessary side effects. In this work, we demonstrate the potential of pH-mediated fluorescence spectroscopy for therapeutic drug monitoring in complex media. We apply this principle to the simultaneous quantification of the chemotherapeutic prodrug Irinotecan and its active metabolite SN-38 from human plasma across the clinically relevant concentration range, i.e. from micromolar to nanomolar at molar ratios of up to 30 : 1.

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A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of paclitaxel and 6α-hydroxy-paclitaxel in human plasma: Development, validation and application in a clinical pharmacokinetic study

Bianca Posocco, Mauro Buzzo, Andrea Follegot, Luciana Giodini, Roberto Sorio, Elena Marangon, Giuseppe Toffoli

Paclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found. Therefore, in order to treat patients with the correct dose of paclitaxel, improving the overall benefit–risk ratio, Therapeutic Drug Monitoring is necessary. In order to quantify paclitaxel and its main metabolite, 6α-hydroxy-paclitaxel, in patients’ plasma, we developed a new, sensitive and specific HPLC–MS/MS method applicable to all paclitaxel dosages used in clinical routine. The developed method used a small volume of plasma sample and is based on quick protein precipitation. The chromatographic separation of the analytes was achieved with a SunFire™ C18 column (3.5 μM, 92 Å, 2,1 x 150 mm); the mobile phases were 0.1% formic acid/bidistilled water and 0.1% formic acid/acetonitrile. The electrospray ionization source worked in positive ion mode and the mass spectrometer operated in selected reaction monitoring mode. Our bioanalytical method was successfully validated according to the FDA-EMA guidelines on bioanalytical method validation. The calibration curves resulted linear (R2 ≥0.9948) over the concentration ranges (1–10000 ng/mL for paclitaxel and 1–1000 ng/mL for 6α-hydroxy-paclitaxel) and were characterized by a good accuracy and precision. The intra- and inter-day precision and accuracy were determined on three quality control concentrations for paclitaxel and 6α-hydroxy-paclitaxel and resulted respectively <9.9% and within 91.1–114.8%. In addition, to further verify the assay reproducibility, we tested this method by re-analysing the incurred samples. This bioanalytical method was employed with success to a genotype-guided phase Ib study of weekly paclitaxel in ovarian cancer patients treated with a wide range of drug’s dosages.

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The right dose in chemotherapy

Silke Krol

Is the goal of an innovative instrument created thanks to a European project

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TriPleX-Based Integrated Optical Ring Resonators for Lab-on-a-Chip and Environmental Detection

Ren´e Heideman, Marcel Hoekman, and Erik Schreuder

In this paper, we report experimental results of integrated optics ring resonators (RRs) based on TriPleX waveguide technology. The RRs operate in the near infrared enabling the use of very cost effective VCSELs as a light source. The experimentally obtained response of the ring resontors is in good agreement with theory, while the measured through and drop responses show very low on-chip losses. The chips show good coupling efficiencies to external fibers due to integrated spotsize convertors. The corresponding signal-to-noise ratio enables for measurements of changes in refractive index (RI) smaller than 1 × 10−6 RIU. The RRs are combined with an 850-nm vertical-cavity surface-emitting laser (VCSEL) as a light source and prototype electronic equipment for signal processing. Several applications are described here, such as RI measurements in fluidic channels, label-free biochemical surface reactions, and gas detection in ambient atmosphere.

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TriPleX: a versatile dielectric photonic platform

Kerstin Wörhoff*, René G. Heideman, Arne Leinse and Marcel Hoekman

Photonic applications based on planar waveguide technology impose stringent requirements on properties such as optical propagation losses, light coupling to optical fibers, integration density, as well as on reliability and reproducibility. The latter is correlated to a high level of control of the refractive index and waveguide geometry. In this paper, we review a versatile dielectric waveguide platform, called TriPleX, which is based on alternating silicon nitride and silicon dioxide films.

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Nanosensors for early cancer detection and for therapeutic drug monitoring

Elisa Salvati, Francesco Stellacci & Silke Krol

The use of nanotechnology for drug delivery in cancer therapy has raised high expectations. Additionally, the use of nanomaterials in sensors to extract and detect tumor specific biomarkers, circulating tumor cells, or extracellular vesicles shed by the tumor holds the promise to detect cancer much earlier and hence improve long-term survival of the patients.

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Poly-l-lysine-Coated Silver Nanoparticles as Positively Charged Substrates for Surface-Enhanced Raman Scattering

Lucia Marsich, Alois Bonifacio, Subhra Mandal, Silke Krol, Claudia Beleites, and Valter Sergo

Positively charged nanoparticles to be used as substrates for surface-enhanced Raman scattering (SERS) were prepared by coating citrate-reduced silver nanoparticles with the cationic polymer poly-l-lysine. The average diameter of the coated nanoparticles is 75 nm, and their zeta potential is +62.3 ± 1.7 mV.

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On the Slow Diffusion of Point-of-Care Systems in Therapeutic Drug Monitoring

Barbara Sanavio and Silke Krol

Recent advancements in point-of-care (PoC) technologies show great transformative promises for personalized preventative and predictive medicine. However, fields like therapeutic drug monitoring (TDM), that first allowed for personalized treatment of patients’ disease, still lag behind in the widespread application of PoC devices for monitoring of patients.

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