A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor

A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a secondgeneration ALK inhibitor, in patient plasma and brain tumor tissue samples. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C_(18) column using a 4-min gradient elution consisting of mobile phase A(0.1% formic acid in water) and mobile phase B(0.1% formic acid in acetonitrile), at a flow rate of 0.4 m L/min. Ceritinib and the internal standard([^(13)C_6]ceritinib) were monitored using multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantitation(LLOQ) was 1 n M of ceritinib in plasma. The calibration curve was linear over ceritinib concentration range of 1–2000 n M in plasma. The intra-and interday precision and accuracy were within the generally accepted criteria for bioanalytical method( o15%).The method was successfully applied to assess ceritinib brain tumor penetration, as assessed by the unbound drug brain concentration to unbound drug plasma concentration ratio, in patients with brain tumors.

All‑Fiber Integrated Thermoelectrically Powered Physiological Monitoring Biosensor

Advanced fabric electronics for long-term personal physiological monitoring,with a self-sufficient energy source,high integrity,sensitivity,wearing comfort,and homogeneous components are urgently desired.Instead of assembling a self-powered biosensor,comprising a variety of materials with different levels of hardness,and supplementing with a booster or energy storage device,herein,an all-fiber integrated thermoelectrically powered physiological monitoring device(FPMD),is proposed and evaluated for production at an industrial scale.For the first time,an organic electrochemical transistor(OECT)biosensor is enabled by thermoelectric fabrics(TEFs)adaptively,sustainably and steadily without any additional accessories.Moreover,both the OECT and TEFs are constructed using a cotton/poly(3,4-ethylenedioxythiophene):poly(styrenesulfon ate)/dimethylsulfoxide/(3-glycidyloxypropyl)trimethoxysilane(PDG)yarn,which is lightweight,robust(90°bending for 1000 cycles)and sweat-resistant(ΔR/R0=1.9%).A small temperature gradient(ΔT=2.2 K)between the environment and the human body can drive the high-gain OECT(71.08 mS)with high fidelity,and a good signal to noise ratio.For practical applications,the on-body FPMD produced an enduring and steady output signal and demonstrated a linear monitoring region(sensitivity of 30.4 NCR(normalized current response)/dec,10 nM~50µM)for glucose in artificial sweat with reliable performance regarding anti-interference and reproducibility.This device can be expanded to the monitoring of various bio-markers and provides a new strategy for constructing wearable,comfortable,highly integrated and self-powered biosensors.