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In this work, two high-performance liquid chromatography (HPLC) assays were developed and validated for the independent determination of edaravone and taurine using 3-methyl-1- p-tolyl-5-pyrazolone and L-glutamine as internal standards. In in vitro experiments, human plasma was separately spiked with a mixture of edaravone and taurine, edaravone or taurine alone. Plasma was precipitated with acetonitrile containing 0.1% formic acid. Ultrafiltration was employed to obtain the unbound ingredients of the two drugs. The factors that might influence the ultrafiltration effiency were elaborately optimized. Plasma supernatant and ultrafiltrate containing taurine were derivated with o-phthalaldehyde and ethanethiol in the presence of 40 mmol/L sodium borate buffer (pH 10.2) at room temperature within 1 min. Chromatographic separations were achieved on an InertSustain C18 column (250 × 4.6 mm, 5 µm). Isocratic 50 mmol/L ammonium acetate-acetonitrile and gradient 50 mmol/L sodium acetate (pH 5.3)-methanol were respectively selected as the mobile phase for the determination of edaravone and taurine. All of the validation data including linearity, extraction recovery, precision, accuracy and stability conformed to the requirements. Results showed that there were no significant alterations in the plasma protein binding rate of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An LC- MS/ MS method was developed and validated for the simultaneous quantification of edaravone and taurine in beagle plasma. The plasma sample was deproteinized using acetonitrile containing formic acid. Chromatographic separations were achieved on an Agilent Zorbax SB-Aq (100 × 2.1 mm, 3.5 μm) column, with a gradient of water (containing 0.03% formic acid) and methanol as the mobile phase at a flow rate of 0.3 mL/min. The analyte detection was carried out in multiple reaction monitoring mode and the optimized precursor-to-product transitions of m/ z [M+H]+ 175.1 → 133.0 (edaravone), m/ z [M+H]+ 189.1 → 147.0 (3-methyl-1- p-tolyl-5-pyrazolone, internal standard, IS), m/ z [M-H]− 124.1→80.0 (taurine), and m/ z [M-H]− 172.0 → 80.0 (sulfanilic acid, IS) were employed to quantify edaravone, taurine, and their corresponding ISs, respectively. The LOD and the lower LOQ were 0.01 and 0.05 μg/mL for edaravone and 0.66 and 2 μg/mL for taurine, respectively. The calibration curves of these two analytes demonstrated good linearity ( r ＞ 0.99). All the validation data including the specificity, precision, recovery, and stability conformed to the acceptable requirements. This validated method has successfully been applied in the pharmacokinetic study of edaravone and taurine mixture in beagle dogs. [ABSTRACT FROM AUTHOR]

Objectives: To create a prognostic model based on differentially expressed genes (DEGs) in early lung squamous cell carcinoma (LUSC) and characterize the relationship between risk scores and tumor immune infiltration., Methods: We identified DEGs in normal and tumor tissues that overlapped between LUSC-related data sets from the Gene Expression Omnibus and the Cancer Genome Atlas and evaluated their roles in the diagnosis and prognosis of LUSC by Kaplan-Meier survival analysis, receiver operating characteristic (ROC) analysis, meta-analysis and nomogram analysis. We then constructed a risk model based on Cox regression analysis and the Akaike information criterion and identified the relationship between LUSC risk scores and immune infiltration., Results: Sixty-two overlapping DEGs were involved with keratinocyte differentiation, epidermal cell differentiation, neutrophil migration, granulocyte chemotaxis, granulocyte migration, leukocyte aggregation, and positive regulation of nuclear factor-κB (NF-κB) activity. Overexpression of family with sequence similarity 83 member A ( FAM83A ) and MYC target 1 ( MYCT1 ), kallikrein related peptidase 8 ( KLK8 ), and downregulation of ADP ribosylation factor like GTPase 14 ( ARL14 ), caspase recruitment domain family member 14 ( CARD14 ), cystatin A ( CSTA ), dickkopf WNT signaling pathway inhibitor 4 ( DKK4 ), desmoglein 3 ( DSG3 ), and keratin 6B ( KRT6B ) were associated with a poor prognosis in LUSC and had significant value for LUSC diagnosis. The expression of CSTA, FAM83A , and MYCT1 and high-risk scores were independent risk factors for a poor prognosis in LUSC. A risk nomogram revealed that risk scores could predict the prognosis of LUSC. The risk score was associated with neutrophils, naive B cells, helper follicular T cells, and activated dendritic cells., Conclusions: The expression levels of CSTA, FAM83A , and MYCT1 are related to the diagnosis and prognosis of LUSC and may have potential as therapeutic targets in LUSC. A risk model and nomogram based on CSTA, FAM83A , and MYCT1 can predict the prognosis of LUSC., Competing Interests: None., (AJTR Copyright © 2022.)