Determination of a novel antifibrotic small molecule GDC‐3280 in human plasma and urine by liquid chromatography tandem mass spectrometry to support its first‐in‐human clinical trial

A specific and robust LC–MS/MS method was developed and validated for the quantitative determination of GDC‐3280 in human plasma and urine. The nonspecific binding associated with urine samples was overcome by the addition of CHAPS. The sample volume was 25 μL for either matrix, and supported liquid extraction was employed for analyte extraction. d6‐GDC‐3280 was used as the internal standard. Linear standard curves (R² > 0.9956) were established from 5.00 to 5000 ng/mL in both matrices with quantitation extended to 50,000 ng/mL through dilution. In plasma matrix, the precision (RSD) ranged from 1.5 to 9.9% (intra‐run) and from 2.4 to 7.2% (inter‐run); the accuracy (RE) ranged from 96.1 to 107% (intra‐run) and from 96.7 to 104% (inter‐run). Similarly, in urine the precision was 1.5–6.2% (intra‐run) and 1.9–6.1% (inter‐run); the accuracy was 83.1–99.3% (intra‐run) and 87.1–98.3% (inter‐run). Good recovery (>94%) and negligible matrix effect were achieved in both matrices. Long‐term matrix stability was established for at least 703 days in plasma and 477 days in urine. Bench‐top stability of 25 h and five freeze–thaw cycles were also confirmed in both matrices. The method was successfully implemented in GDC‐3280's first‐in‐human trial for assessing its pharmacokinetic profiles.     

Bootstrap robust prescriptive analytics

Mathematical Programming - We address the problem of prescribing an optimal decision in a framework where the cost function depends on uncertain problem parameters that need to be learned from...     

Use of TLC-Densitometric Method for Determination of Valproic Acid in Capsules

Determination of valproic acid in the drug was carried out on the aluminum silica gel 60F₂₅₄ plates and using acetone–water–chloroform–ethanol–ammonia at a volume ratio of 30:1:8:5:11 as the mobile phase, respectively. Two methods of detection of valproic acid were used. The first was a 2% aqueous CuSO₄×5H₂O solution, and the second was a 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system. The applied TLC-densitometric method is selective, linear, accurate, precise, and robust, regardless of the visualizing reagent used for the determination of valproic acid in Convulex capsules. It has low limits of detection (LOD) and limits of quantification (LOQ), which are equal to 5.8 μg/spot and 17.4 μg/spot using a 2% aqueous CuSO₄×5H₂O solution as visualizing agent and also 0.32 μg/spot and 0.97 μg/spot using a 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system as visualizing reagent, respectively. The described analytical method can additionally be used to study the identity of valproic acid in a pharmaceutical preparation. The linearity range was found to be 20.00–80.00 μg/spot and 1.00–2.00 μg/spot for valproic acid detected on chromatographic plates using a 2% aqueous CuSO₄×5H₂O solution and the 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system, respectively. A coefficient of variation that was less than 3% confirms the satisfactory accuracy and precision of the proposed method. The results of the assay of valproic acid equal 96.2% and 97.0% in relation to the label claim that valproic acid fulfill pharmacopoeial requirements. The developed TLC-densitometric method can be suitable for the routine analysis of valproic acid in pharmaceutical formulations. The proposed TLC-densitometry may be an alternative method to the modern high-performance liquid chromatography and square wave voltammetry in the control of above-mentioned substances, and it can be applied when other analytical techniques is not affordable in the laboratory.     

Laser marked shadowgraphy: a novel optical planar technique for the study of microbubbles and droplets

A novel combination of backlighting and glare point velocimetry and sizing (GPVS) is proposed to measure the size distribution of microbubbles (or microdroplets). This new technique, which we will call laser marked shadowgraphy, avoids sizing out-of-focus bubbles (or droplets) and the associated bias error. Compared to backlighting, this combination also improves the precision of the diameter measurement and allows void fraction measurements. Compared with GPVS, a more robust image processing is obtained. The applicability of the developed technique is demonstrated on a cloud of electrochemically generated hydrogen bubbles.     

Ion generation from Al-laser-produced plasma

Particle diagnostics of Al-laser-produced plasma based on ion collectors identified three groups of emitted ions. Their velocity distributions were analyzed to obtain the mean ion energy, energy and charge carried by ions, including the angular distributions of these quantities. The electron temperature evaluated from these measurements was compared with X-ray results. A satisfactory agreement between the two sets of data was found. In both the cases the electron temperature grows only very slowly with the incident laser power. Origin of different ion groups is discussed. Iodine photodissociation laser system PERUN was used as a driver.     

Magnesium chloride modified with organoaluminium compounds as a support of the zirconocene catalyst for ethylene polymerisation

This work describes the influence of the modification of the MgCl₂(THF)₂ and MgCl₂ magnesium supports with the AlEt₂Cl, MAO, AlEt₃, AlMe₃, and AlEt₂Cl alkylaluminium compounds on heterogenisation of the bis(cyclopentadienyl) zirconium(IV) dichloride Cp₂ZrCl₂ catalyst. It was found that only the MgCl₂(THF)₂ support modified with AlEt₂Cl gave the heterogeneous catalyst. On the contrary, application of a magnesium carrier modified by AlEt₃, AlMe₃, and MAO compounds only results in a homogeneous zirconocene catalyst.     

Study of Lipophilicity and Application of Selected Structural Descriptors in QSAR Analysis of Nicotinic Acid Derivatives. Investigations on RP18WF254 Plates. Part II

JPC – Journal of Planar Chromatography – Modern TLC - Nicotinic acid (NAC) and its derivatives methyl nicotinate (MN), ethyl nicotinate (EN), isopropyl nicotinate (IPN), butyl...     

Investigation of the effect of plasma waves excitation on target normal sheath ion acceleration using fs laser‐irradiating hydrogenated structures

Measurements of ion acceleration in polymethylmethacrylate foils covered by a thin copper film irradiated by fs laser in target normal sheath acceleration regime are presented. The ion acceleration depends on the laser parameters, such as the pulse energy; depends on the irradiation conditions, such as the focal point position of the laser with respect to the target surface; and depends on the target properties, such as the metallic film thickness. The proton acceleration increases in the presence of the metallic film enhancing the plasma electron density, reaching about 1.6 MeV energy for a focal position on the target surface. The plasma diagnostics uses SiC detectors, absorber foils, Faraday cups, and gafchromic films. Employing p‐polarized laser light and a suitable oblique incidence, it is possible to increase the proton acceleration up to about 2.0 MeV thanks to the effects of laser absorption resonance due to plasma waves excitation.     

Attomole-per Cell Atomic Mass Spectrometry Measurement of Platinum and Gold Drugs in Cultured Lung Cancer Cells

In this study, we developed a strategy to determine atto- and femtomolar amounts of metal ions in lysates and mineralizates of cells (human non-small-cell lung carcinoma (NSCLC, A549) and normal lung (MRC-5)) exposed to cytotoxic metallo-drugs: cisplatin and auranofin at concentrations close to the half-maximal inhibitory drug concentrations (IC₅₀). The developed strategy combines data obtained using biological and chemical approaches. Cell density was determined using two independent cell staining assays using trypan blue, calcein AM/propidium iodide. Metal concentrations in lysed and mineralized cells were established employing a mass spectrometer with inductively coupled plasma (ICP-MS) and equipped with a cross-flow nebulizer working in aspiration mode. It allowed for detecting of less than 1 fg of metal per cell. To decrease the required amount of sample material (from 1.5 mL to ~100 µL) without loss of sensitivity, the sample was introduced as a narrow band into a constant stream of liquid (flow-injection analysis). It was noticed that the selectivity of cisplatin accumulation by cells depends on the incubation time. This complex is accumulated by cells at a lower efficiency than auranofin and is found primarily in the lysate representing the cytosol. In contrast, auranofin interacts with water-insoluble compounds. Despite their different mechanism of action, both metallo-drugs increased the accumulation of transition metal ions responsible for oxidative stress.