Lenvatinib is a multi-targeted tyrosine kinase inhibitor that inhibits tumor angiogenesis, but hypertension is the most common adverse reaction. Telmisartan is an angiotensin receptor blocker used to ...treat hypertension. In this study, a simple ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of lenvatinib and telmisartan, and it was applied to the pharmacokinetic drug interaction study. Plasma samples were treated with acetonitrile to precipitate protein. Water (containing 5 mM of ammonium acetate and 0.1% formic acid) and acetonitrile (0.1% formic acid) were used as the mobile phases to separate the analytes with gradient elution using a column XSelect HSS T3 (2.1 mm × 100 mm, 2.5 μm). Multiple reaction monitoring in the positive ion mode was used for quantification. The method was validated and the precision, accuracy, matrix effect, recovery, and stability of this method were reasonable. The determination of analytes was not interfered with by other substances in the blank plasma, and the calibration curves of lenvatinib and telmisartan were linear within the range of 0.2-1000 ng/mL and 0.1-500 ng/mL, respectively. The results indicate that lenvatinib decreased the systemic exposure of telmisartan. Potential drug interactions were observed between lenvatinib and telmisartan.
In this study, polystyrene nanofibers were prepared by electrospinning for the adsorption of olanzapine, risperidone, and clozapine from aqueous solution. The properties of polystyrene nanofibers ...were characterized via FTIR, SEM, TEM, TG, and XRD analyses. In addition, the impact of contact time, initial ion concentration, adsorbent dosage, temperature, and pH on the adsorption was studied. The adsorption kinetics and thermodynamic evaluation of three analytes on PS nanofibers were performed. The adsorption of the three analytes by polystyrene nanofibers followed the first-order kinetics with constant rates of 0.02348, 0.02683, and 0.03024 mg/g min for olanzapine, risperidone, and clozapine, respectively. Further, the adsorption conformed to Redlich-Peterson isotherm model and the maximum adsorption capacities for olanzapine, risperidone, and clozapine were 12.33, 8.36, and 12.96 mg/g, respectively. The adsorption process was characterized by spontaneous, exothermic, and physical reaction. The regeneration of nanofiber adsorbent showed that the adsorption capacity did not significantly change after 5 cycles of desorption. The selectivity of different analytes followed the order of clozapine > risperidone > olanzapine. Thus, the polystyrene electrospun nanofibers exhibit good potential as novel adsorbents for the isolation and purification of antipsychotic drugs from biological samples.
Motivation: The generation of large amounts of microarray data and the need to share these data bring challenges for both data management and annotation and highlights the need for standards. MIAME ...specifies the minimum information needed to describe a microarray experiment and the Microarray Gene Expression Object Model (MAGE-OM) and resulting MAGE-ML provide a mechanism to standardize data representation for data exchange, however a common terminology for data annotation is needed to support these standards. Results: Here we describe the MGED Ontology (MO) developed by the Ontology Working Group of the Microarray Gene Expression Data (MGED) Society. The MO provides terms for annotating all aspects of a microarray experiment from the design of the experiment and array layout, through to the preparation of the biological sample and the protocols used to hybridize the RNA and analyze the data. The MO was developed to provide terms for annotating experiments in line with the MIAME guidelines, i.e. to provide the semantics to describe a microarray experiment according to the concepts specified in MIAME. The MO does not attempt to incorporate terms from existing ontologies, e.g. those that deal with anatomical parts or developmental stages terms, but provides a framework to reference terms in other ontologies and therefore facilitates the use of ontologies in microarray data annotation. Availability: The MGED Ontology version.1.2.0 is available as a file in both DAML and OWL formats at . Release notes and annotation examples are provided. The MO is also provided via the NCICB's Enterprise Vocabulary System (). Contact:Stoeckrt@pcbi.upenn.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Owing to the adverse effects of the overuse of common sedative-hypnotics on human health, the development of an efficient analytical method for the detection of drugs in clinical emergencies and ...forensic science is significant. Although conventional analytical methods, such as immunoassay, liquid chromatography (LC), gas chromatography, and mass spectrometry (MS) are reliable, they exhibit drawbacks such low-throughput screening and high costs. Thus, in this study, we developed a novel high-throughput method consisting of a polystyrene-based solid phase extraction (SPE) and an LC with tandem MS analysis for the detection of drugs in biological samples and investigated its precision and reliability via the detection of twelve sedative-hypnotics in human urine and plasma samples. Good linear relationship (r ≥ 0.99) were achieved within the concentration range of 0.1–20 ng/mL for the 12 analytes in urine samples. Whereas, in the plasma samples, the correlation coefficient was greater than 0.99 in the concentration range 1–100 ng/mL for lorazepam and clonazepam and in the range 0.5–100 ng/mL for the remaining analytes. The intra- and inter-day precision, autosampler and freeze–thaw stabilities, and lower limit of quantitation (LLOQ) for all twelve analytes in the urine and plasma samples were favorable. Furthermore, sedative-hypnotics were detected in clinical samples obtained from the Hebei General Hospital using this method. These results indicated that the analytical method proposed in this study can be effectively applied in toxicology screening and drug abuse monitoring.The method developed in this study could be applied in clinical and forensic toxicology laboratories for sedative-hypnotic drug screening, providing support for drug abuse monitoring and clinical diagnosis.
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•Ps nanofibers proved to be effective sorbent for sedative-hypnotic medications.•A high-throughput Ps nanofibers-based μ-SPE along with LC-MS/MS method was developed.•The method was successfully applied in fast preparation and detection of actual plasma/urine samples.
A novel extraction procedure was developed using polystyrene (PS) nanofibers as a solid-phase extraction sorbent to collect atypical antipsychotics (AAPs) from human plasma. The extraction targets ...were then monitored by ultra high performance liquid chromatography with an ultraviolet detector system. Parameters affecting extraction efficiency such as fiber packing amount, wash solution, and eluted solvent were investigated. Under optimized conditions, the linear range of seven AAPs was 1-50 μgmL
−1
(
R
2
> 0.996). Inter-day and intra-day relative standard deviations were less than 15.1%, and relative error varied from −17.1% to 12.0%. Furthermore, 50.5-79.3% extraction recoveries were obtained. The lower limit of quantification was 1 μg mL
−1
, and detection limit was 0.5 μg mL
−1
. The method developed in this study may be applied to simultaneous quantification of seven AAPs in human plasma due to its simplicity, selectivity, and efficiency.
A novel extraction procedure was developed using electrospun polystyrene (PS) nanofibers as a solid-phase extraction sorbent to collect atypical antipsychotics (AAPs) from human plasma.
•An UPLC-MS/MS method was developed for the determination of lenvatinib in rats.•The method was applied to evaluate the pharmacokinetics of lenvatinib in rats.•The effect of Wuzhi capsule on the ...pharmacokinetics of lenvatinib was evaluated.•Drug–drug interactions might exist between the two drugs.
Lenvatinib (LEN) is a multitargeted tyrosine kinase inhibitor registered for the first-line treatment of unresectable advanced hepatocellular carcinoma. Wuzhi capsule (WZC) is a traditional Chinese medicine preparation; it is used to decrease the aminotransferase level of the liver and protect liver function. Thus, patients with hepatocellular carcinoma (HCC) are potentially treated with a combination of LEN and WZC, but there is no information about the interaction between the two drugs. We developed a simple, rapid, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method for the quantitative determination of lenvatinib in rat plasma. Liquid–liquid extraction of plasma samples was carried out with ethyl acetate. Chromatographic separation of analyte was performed using gradient elution with acetonitrile and 0.1% formic acid water. The positive ion multi-response monitoring mode was used, and the target of the parent and daughter ions of LEN and IS were m/z 427.1→370 and m/z 432.1→370, respectively. All the validation projects were in accordance with the guidelines. Good linearity of 0.2–1000 ng/mL (r > 0.999) was achieved. The lower limit of quantification was 0.2 ng/mL. The precision and accuracy are acceptable. The method was successfully applied to pharmacokinetics and drug interaction analysis. The results show that WZC can significantly increase the Cmax (maximum plasma concentration) and AUC (area under the concentration-time curve) of LEN. An UPLC -MS/MS method that can be used for studying drug–drug interaction as a valuable tool was developed in this study. Drug-drug interactions were observed between the WZC and LEN.
A UPLC–MS/MS method was developed to determine the levels of five traditional antipsychotics (APs) (chlorprothixene, perphenazine, fluphenazine, thioridazine, and promethazine) in human plasma with ...carbamazepine as the internal standard. Samples were extracted using simple liquid–liquid extraction (ethyl acetate/methyl tert‐butyl ether, 2:3 v/v); then the analytes were subjected to gradient elution chromatography with a mobile phase composed of 0.1% formic acid in water and acetonitrile. The analytes were separated using a Waters XBridge BEH C18 column (100 × 2.1 mm, 2.5 μm). The linear ranges of chlorprothixene, perphenazine, fluphenazine, thioridazine, and promethazine are 2–250 ng/mL, r > 0.995. The limit of quantitation is 2 ng/mL, and the limit of detection is in the range of 0.1–0.5 ng/mL. The inter‐day and intra‐day relative standard deviations are less than 10%, and the relative errors are in the range of −5.70 to 7.20%. The recoveries of the five drugs are in the range of 70–109%. The results of methodology verification indicate that this method is simple, economical, sensitive, and suitable for the simultaneous quantification of five traditional APs in human plasma.
Almonertinib was included in the first‐line treatment of non‐small cell lung cancer with EGFR T790M mutations by the Chinese Society of Clinical Oncology in 2021. Considering that immunocompromised ...lung cancer patients are prone to opportunistic fungal infections, and most triazole antifungal drugs are moderate or strong inhibitors of CYP3A4, this study was conducted to develop and validate an accurate and rapid ultra‐performance liquid chromatography tandem mass spectrometry method for quantifying almonertinib in plasma and for investigating the pharmacokinetic changes of almonertinib caused by voriconazole and fluconazole in rats. After liquid–liquid extraction with tert‐butyl methyl ether, an XSelect HSS T3 column (2.1 × 100 mm, 2.5 μm, Waters) was used for the chromatographic separation of almonertinib and sorafenib‐D3 (internal standard). The analytes were detected using an AB Sciex Triple Quad 5,500 mass spectrometer in the positive ionization mode. The method exhibited great linearity (0.5–200 ng/ml, r > 0.997) and stability under the established experimental conditions. All validation experiments were in accordance with the guidelines, and the results were all within the acceptable limits. This method was successfully applied to the researches of pharmacokinetics and drug interactions for almonertinib in rats. Voriconazole and fluconazole significantly altered the pharmacokinetic profiles of almonertinib and increased the systemic exposure of almonertinib in rats to different degrees, but further human trials should be conducted to validate the results.
The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains ...are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource (http://obi-ontology.org) providing details on the people, policies, and issues being addressed in association with OBI. The current release of OBI is available at http://purl.obolibrary.org/obo/obi.owl.
Neuroblastoma is the second most common solid malignancy of childhood. Enhanced expression of the amplified N-myc gene in the tumor cells may be associated with poor patient prognosis and may ...contribute to tumor development and progression. The use of deferoxamine mesylate (DFO), an iron chelator, to treat neuroblastoma is being investigated in national clinical studies. We show here by TUNEL assay and DNA laddering that DFO induces apoptosis in cultured human neuroblastoma cells, which is preceded by a decrease in the expression of N-myc and the altered expression of some other oncogenes (up-regulating c-fos and down-regulating c-myb) but not housekeeping genes. The decrease in N-myc expression is iron-specific but does not result from inhibition of ribonucleotide reductase, because specific inhibition of this iron-containing enzyme by hydroxyurea does not affect N-myc protein levels. Nuclear run-on and transient reporter gene expression experiments show that the decrease in N-myc expression occurs at the level of initiation of transcription and by inhibiting N-myc promoter activity. Comparison across neuroblastoma cell lines of the amount of residual cellular N-myc protein with the extent of apoptosis measured as pan-caspase activity after 48 h of iron chelation reveals no correlation, suggesting that the decrease in N-myc expression is unlikely to mediate apoptosis. In conclusion, chelation of cellular iron by DFO may alter the expression of multiple genes affecting the malignant phenotype by multiple pathways. Given the clinical importance of N-myc overexpression in neuroblastoma malignancy, decreasing N-myc expression by DFO might be useful as an adjunct to current
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