Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Seismic Performance Assessment of Water Distribution Systems Based on Multi-Indexed Nodal Importance

open access articleSeismic performance assessment of water distribution systems (WDSs) based on hydraulic simulation is essential for resilience evaluation of WDSs under earthquake disasters. The assessment is mainly to determine how the water supply will be affected due to pipe breaks caused by the earthquake, with the water supply loss estimated based on the loss of supply to nodes. Existing research works usually use the average or overall performance metric of all user nodes as the system performance indicator without considering user nodes' individual performance and criticality. This paper proposes a framework to evaluate the importance of user nodes considering post-earthquake rescue service and the seismic performance of individual user nodes in the WDS, which supports the pipeline renovation plan to improve the performance of critical user nodes. The importance of user nodes is evaluated by a multi-index model, including the indices for daily service, post-earthquake rescue service, and network topology influence of user nodes. These indices evaluate the importance of user nodes in terms of their roles for daily water service, emergent rescue service, and water transmission to other nodes, respectively. Fragility model of pipelines evaluates the earthquake-induced damages of the WDS, and the seismic performance assessment of the WDS system is performed by the hydraulic model of the WDS with pipeline damages. The proposed framework is implemented in an actual WDS; the results show that the importance classification to user nodes by multi-index approach can identify the critical user nodes for post-earthquake rescue service, which traditional methods may ignore. The importance classification and seismic performance of individual user nodes make it feasible to check the seismic performance of critical user nodes and formulate a targeted pipeline renovation plan to focus limited resources on critical user nodes

Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Case report: Multiple arterial stenoses induced by autosomal-recessive hypophosphatemic rickets type 2 associated with mutation of ENPP1: a case study

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1)-related multiple arterial stenoses is a rare clinical syndrome in which global arterial calcification begins in infancy, with a high probability of early mortality, and hypophosphatemic rickets develops later in childhood. The vascular status of an ENPP1-mutated patient when they enter the rickets phase has not been thoroughly explored. In this study, we presented a case of an adolescent with an ENPP1 mutation who complained of uncontrolled hypertension. Systematic radiography showed renal, carotid, cranial, and aortic stenoses as well as random calcification foci on arterial walls. The patient was incorrectly diagnosed with Takayasu’s arteritis, and cortisol therapy had little effect on reducing the vascular stenosis. As a result, phosphate replacement, calcitriol substitution, and antihypertensive medication were prescribed, and the patient was discharged for further examination. This research presented the vascular alterations of an ENPP1-mutanted patient, and while there is less calcification, intimal thickening may be the primary cause of arterial stenosis

Prediction of Creep Curves Based on Back Propagation Neural Networks for Superalloys

Creep deformation is one of the main failure forms for superalloys during service and predicting their creep life and curves is important to evaluate their safety. In this paper, we proposed a back propagation neural networks (BPNN) model to predict the creep curves of MarM247LC superalloy under different conditions. It was found that the prediction errors for the creep curves were within ±20% after using six creep curves for training. Compared with the θ projection model, the maximum error was reduced by 30%. In addition, it is validated that this method is applicable to the prediction of creep curves for other superalloys such as DZ125 and CMSX-4, indicating that the model has a wide range of applicability

N-cadherin expression is associated with acquisition of EMT phenotype and with enhanced invasion in erlotinib-resistant lung cancer cell lines.

BACKGROUND: The epidermal growth-factor receptor tyrosine kinase inhibitors have been effective in non-small cell lung cancer patients. However, acquired resistance eventually develops in most patients despite an initial positive response. Emerging evidence suggests that there is a molecular connection between acquired resistance and the epithelial-mesenchymal transition (EMT). N-cadherin is involved in the EMT and in the metastasis of cancer cells. Here, we analyzed N-cadherin expression and function in erlotinib-resistant lung cancer cell lines. METHODS: H1650 cell lines were used to establish the subline resistant to erlotinib(H1650ER). Then, induction of the EMT was analyzed using immunostaining and western blots in H1650ER cells. N-cadherin expression in the resistant cells was examined using FACS and western blot. In addition, an invasion assay was performed to characterize the resistant cells. The effects of N-cadherin on cell proliferation and invasion were analyzed. The association of N-cadherin expression with the EMT phenotype was investigated using immunohistochemical analysis of 13 archived, lung adenocarcinoma tissues, before and after treatment with erlotinib. RESULTS: In H1650ER cells, N-cadherin expression was upregulated, paralleled by the reduced expression of E-cadherin. The marked histological change and the development of a spindle-like morphology suggest that H1650ER cells underwent an EMT, accompanied by a decrease in E-cadherin and an increase in vimentin. A change in the EMT status between pre-and post-treatment was observed in 11 out of 13 cases (79%). In biopsies of resistant cancers, N-cadherin expression was increased in 10 out of 13 cases. Induction of the EMT was consistent with aggressive characteristics. Inhibition of N-cadherin expression by siRNA was tested to reduce proliferation and invasion of H1650ER cells in vitro. CONCLUSIONS: Our data provide evidence that induction of the EMT contributes to the acquired resistance to EGFR-TKIs in lung cancer. It suggests that N-cadherin is a potential molecular target in the treatment of NSCLC

A σ phase-γ phase orientation relationship observed in solidification of the 7Mo super-austenitic stainless steel

In-situ observation and microstructure analysis were combined with the nanoindentation to study the effect of the orientation relationship between the σ and γ phases on the mechanical property of the 7Mo super austenite stainless steel. The results from the HRTEM and the nanoindentation indicate that the semi-coherent interface (111)γ // (001)σ (which is composed of several atomic layers in the absence of element segregation) produced by eutectic transformation, effectively improves the strength of the interface

Glycopolymer Grafted Silica Gel as Chromatographic Packing Materials

The modification of the surface of silica gel to prepare hydrophilic chromatographic fillers has recently become a research interest. Most researchers have grafted natural sugar-containing polymers onto chromatographic surfaces. The disadvantage of this approach is that the packing structure is singular and the application scope is limited. In this paper, we explore the innovative technique of grafting a sugar-containing polymer, 2-gluconamidoethyl methacrylamide (GAEMA), onto the surface of silica gel by atom transfer radical polymerization (ATRP). The SiO2-g-GAEMA with ATRP reaction time was characterized by Fourier infrared analysis, Thermogravimetric analysis (TGA), and elemental analysis. As the reaction time lengthened, the amount of GAEMA grafted on the surface of the silica gel gradually increased. The GAEMA is rich in amide bonds and hydroxyl groups and is a typical hydrophilic chromatography filler. Finally, SiO2-g-GAEMA (reaction time = 24 h) was chosen as the stationary phase of the chromatographic packing and evaluated with four polar compounds (uracil, cytosine, guanosine, and cytidine). Compared with unmodified silica gel, modified silica gel produces sharper peaks and better separation efficiency. This novel packing material may have a potential for application with highly isomerized sugar mixtures

Highly Dispersed Antisintering Cu Catalyst from Cu–Al Spinel Oxide Obtained by Using Surface Solid Reaction for Reverse Water–Gas Shift

Inhibiting the sintering of Cu-based catalysts for CO2 reverse water–gas shift (RWGS) reaction is still a great challenge. Herein, Cu–Al spinel supported on Al2O3 was prepared by a surface solid reaction and used as a precursor to obtain Cu particles with high dispersions and high stabilities. Due to the high dispersions of Cu cations in Cu–Al spinel, strong chemical interactions between Cu particles and newly generated Al2O3, and the isolation effects of Al2O3 particles, Cu particles derived from Cu–Al spinel exhibited smaller sizes after H2 reduction, excellent activities, and 300 h stabilities for RWGS reactions. However, Cu particles obtained from the supported CuO precursor showed much larger particle sizes (>70 nm) and inferior activities and stabilities for CO2 reverse water–gas shift reaction. This study made a successful attempt to enhance the activities and stabilities of Cu-based catalysts through changing the oxide precursor