Determination of ketamine in rabbit plasma by gradient elution liquid chromatography/electrospray mass spectrometry

A sensitive and simple liquid chromatography/electrospray mass spectrometry (LC-ESI-MS) method for determination of ketamine in rabbit plasma using one-step protein precipitation was developed and validated. After addition of methadone as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographically separation was achieved on an SB-C18 (2.1 mm × 50 mm, 3.5 μm) column with methanol-0.1 % formic acid as the 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 237.7 → 219.7 for ketamine and m/z 309.9 → 264.8 for the IS. Calibration plots were linear over the range of 5-1000 ng/mL for ketamine in rabbit plasma. Lower limit of quantification (LLOQ) for ketamine was 5 ng/mL. Mean recovery of ketamine from plasma was in the range of 97.5-100.1 %. RSD of intra-day and inter-day precision were both less than 11 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of ketamine in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of ketamine in rabbit plasma by gradient elution liquid chromatography/electrospray mass spectrometry

A sensitive and simple liquid chromatography/electrospray mass spectrometry (LC-ESI-MS) method for determination of ketamine in rabbit plasma using one-step protein precipitation was developed and validated. After addition of methadone as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographically separation was achieved on an SB-C18 (2.1 mm × 50 mm, 3.5 μm) column with methanol-0.1 % formic acid as the 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 237.7 → 219.7 for ketamine and m/z 309.9 → 264.8 for the IS. Calibration plots were linear over the range of 5-1000 ng/mL for ketamine in rabbit plasma. Lower limit of quantification (LLOQ) for ketamine was 5 ng/mL. Mean recovery of ketamine from plasma was in the range of 97.5-100.1 %. RSD of intra-day and inter-day precision were both less than 11 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of ketamine in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Influence of AC voltage on the positive DC corona current pulses in a wire-cylinder gap View Document

In the development of hybrid HVDC and HVAC transmission lines, the study of radio interference is an important issue. Positive corona current pulses from high voltage transmission lines are the main source of radio interference. In this paper, the design of a wire-cylinder gap electrode system is presented to study the influence of AC voltage on the characteristics of positive corona current pulses. The study shows that the mode of the current pulses is different from that of either DC or AC corona discharge. Waveform parameters of the pulses, such as rise time, half wave time, duration time, repetition rates, average amplitude, and time intervals of secondary pulses are all statistically analyzed in this study. The empirical formulas for the repetition rates with different AC voltages are presented. A theoretical explanation based on an ion cloud model is given to reveal the mechanism behind the influence of AC voltage on positive corona discharge. The experimental results could provide some references for the prediction of radio interference from hybrid AC/DC transmission lines

Pharmacokinetics and tissue distribution of N-3- methoxybenzyl-palmitamide in rat: A macamide derived from Lepidium meyenii

Purpose: To study the pharmacokinetics and tissue distribution of N-3-methoxybenzyl-palmitamide (MPM) derived from Lepidium meyenii (Maca)Methods: MPM and N-benzylpalmitamide (BPM, as the internal standard, IS) were prepared by one-pot synthesis method and characterized. For the analysis of MPM in rat plasma and tissue samples, a rapid ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method was developed and validated by optimizing sample preparation conditions and UPLC conditions. Finally, the pharmacokinetics and biodistribution of MPM after oral administration in rats were studied.Results: The lower limit of quantification (LLOQ) and limit of detection (LOD) of the UPLC-MS/MS method were 1.2 and 5.0 ng/mL, respectively. Good linear relationship of calibration curve (r > 0.9951) was achieved over the range of 5 – 5000 ng/mL. In pharmacokinetics, plasma concentration-time curve of MPM showed double peaks. The highest distribution of MPM after absorption was in the stomach, followed by lung. The absorption and eliminate rate of MPM were slow in rats. In fact, MPM displayed a lung targeting property.Conclusion: The developed UPLC-MS/MS method is suitable for plasma and tissue distribution studies of MPM in rats. The present study can provide guidance for the further development and utilization of Maca tuber.Keywords: Macamide, Maca tuber, Lepidium meyenii, Pharmacokinetics, Tissue distribution, UPLCMS/M

Limnodrilus simplex sp nov (Oligochaeta: Naididae: Tubificinae) from Changjiang River, China

Limnodrilus simplex sp. nov. (Oligochaeta: Naididae: Tubificinae) is described based on a single specimen from the mainstream of the Changjiang River near Anqing City, Anhui Province, China. The new species is assigned to Limnodrilus by the presence of long vasa deferentia, spindle-shaped atria with long ejaculatory ducts, large prostate glands, and thick cylindrical penial sheaths. It differs from its congeners in having simple-pointed chaetae and cuticularized penial sheaths without hoods. Limnodrilus simplex is closer to L. paramblysetus and L. amblysetus in possessing penial sheaths with relatively low length/maximum width ratio

Scenarios of temporal environmental alterations and phytoplankton diversity in a changing bay in the East China Sea

In the context of global change, the stressors of warming and eutrophication have significant ecological implications in coastal waters. In order to examine the diversity of phytoplankton and its relationship with water quality, we conducted a survey of phytoplankton community compositions and their correlation with environmental changes over four seasons in a eutrophic bay located in the East China Sea. Through a systematic analysis, we identified diatoms and dinoflagellates as the primary dominant groups, with the species Skeletonema costatum, Skeletonema marinoi, Biddulphia sinensis, Thalassiosira eccentrica, Leptocylindrus danicus, Coscinodiscus oculus-iridis, Coscinodiscus jonesianus, and Chaetoceros knipowitschi as the most abundant species in all seasons. Significant seasonal alterations were observed in both environmental settings and phytoplankton species richness, dominance, and abundance. The phytoplankton community varied in its response to diverse aquatic environments and was principally affected by temperature, silicic acid concentrations, and suspended solids. Elevated temperatures were found to promote an increase in phytoplankton abundance. However, no clear evidence of diatom and dinoflagellate succession in relation to N:P ratio was observed across seasons. Water quality analysis illustrated that the majority of the study area exhibited a mid-eutrophic with severe organic pollution. The abundance of phytoplankton was significantly influenced by eutrophication and organic pollution. The accelerated warming process related to coastal nuclear power plants and nutrient regime alterations significantly affect the temporal shift of the phytoplankton community. These findings contribute valuable insights into the effects of eutrophic environments on the structure of phytoplankton communities in coastal aquatic systems

Determination of tolbutamide in rabbit plasma by LC-MS/MS and its application to pharmacokinetic study

A sensitive and selective liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for the determination of tolbutamide in rabbit plasma was developed and validated over the concentration range of 4-1000 ng mL-1. After addition of bupivacaine as internal standard (IS), a simplified protein precipitation with acetonitrile was employed for the sample preparation. Chromatographic separation was performed by an Agilent Zorbax SB-C18 column (150 mmu2.1 mm, 3.5 um). The mobile phase was acetonitrile-1% formic acid in water (50:50 v/v) delivered at a flow rate of 0.3 mL min-1. The MS data acquisition was accomplished by multiple reactions monitoring (MRM) mode with positive electrospray ionization (ESI) interface. The lower limit of quantification (LLOQ) was 4 ng mL-1. For interday and intra-day tests, the precision (RSD) for the entire validation was less than 10%, and the accuracy was within the 94.7% to 105.6% range. The validated method is successfully used to analyze the drug in samples of rabbit plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of esomeprazole in rabbit plasma by liquid chromatography-mass spectrometry and its application to a pharmacokinetic study

A sensitive and selective liquid chromatography-mass spectrometry (LC–MS) method for determination of esomeprazole in rabbit plasma was developed and validated. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation, and chromatography involved Agilent SB-C18 column (2.1 x 150 mm, 5.0 μm) using 0.1 % formic acid in water and acetonitrile as a mobile phase with gradient elution. Detection involved positive ion mode electrospray ionization (ESI), and selective ion monitoring (SIM) mode was used for quantification of target fragment ions m/z 198 for esomeprazole and m/z 326 for midazolam (internal standard, IS). The assay was linear over the range of 10–2000 ng/mL for esomeprazole, with a lower limit of quantitation (LLOQ) of 10 ng/mL for esomeprazole. Intra- and inter-day precisions were less than 14 % and the accuracies were in the range of 89.2-112.6 % for esomeprazole. This developed method was successfully applied for the determination of esomeprazole in rabbit plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents

Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks.Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-α in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers.Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-α, and hindered cell migration. In addition, at concentrations of 1, 2, and 4 μM, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6-dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties.Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-α. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study’s mechanistic exploration, highlighting B7’s simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression