Correction to: Development of a simultaneous LC-MS/MS method to predict in vivo drug-drug interaction in mice.

The author would like to change conflict of interest statement of the online published article.

Development of a simultaneous LC-MS/MS method to predict in vivo drug-drug interaction in mice.

Cocktail substrates are useful in investigating drug-drug interactions (DDI) that can rapidly identify the cytochrome P450 (CYP) isoforms that interact with test drugs. In this study, we developed and validated five probe drugs for CYP1A, CYP2B, CYP2C, CYP2D, and CYP3A using LC-MS/MS to determine CYP activities in mice. The five probe substrates were caffeine (2 mg/kg), bupropion (30 mg/kg), omeprazole (4 mg/kg), dextromethorphan (40 mg/kg), and midazolam (2 mg/kg) for CYP1A, CYP2B, CYP2C, CYP2D, and CYP3A, respectively. The cocktail substrates were orally administered to male 5-week-old ICR mice over 0-240 min. The analytical method was validated; it showed high selectivity, linearity, and acceptable accuracy. We confirmed the lack of interaction of this cocktail in the control state (no effect of CYP inducer or inhibitor) and suggested AUCratio (metabolite/substrate) as a unit to evaluate DDI in vivo. In addition, the cocktail assay was applied for the determination of pharmacokinetic parameters against phenobarbital as a selective CYP2B inducer and ketoconazole as a strong CYP3A inhibitor. The concentration of cocktail substrates and the LC-MS/MS method were optimized. In conclusion, we developed a simultaneous and comprehensive analysis system for predicting potential DDI in mice.

Non-targeted metabolomics-guided sildenafil metabolism study in human liver microsomes.

Metabolomics combined with high-resolution mass spectrometry (HR-MS) and multivariate data analysis has broad applications in the study of xenobiotic metabolism. Although information about xenobiotic metabolism is essential to understand toxic mechanisms, pharmacokinetic parameters and excretion pathways, it is limited to predict all generated metabolites in biological fluids. Here, we revisited sildenafil metabolism in human liver microsomes using a metabolomics approach to achieve a global picture of sildenafil phase 1 metabolism. Finally, 12 phase 1 metabolites were identified in human liver microsomes; M1-M5 were previously known metabolites. The chemical structures of the novel metabolites were elucidated by MS2 fragmentation using an HR-MS system as follows: M6, reduced sildenafil; M7, N,N-deethylation and mono-oxidation; M8, demethanamine, N,N-deethylation and mono-hydroxylation; M9, demethanamine and N,N-deethylation; M10 and M11, mono-oxidation in the piperazine ring after N-demethylation; and M12, mono-oxidation. All metabolites, except M1, were formed by CYP3A4 and CYP3A5. In conclusion, we successfully updated the metabolic pathway of sildenafil in human liver, including 7 novel metabolites using metabolomics combined with HR-MS and multivariate data analysis.

Gaseous Nanocarving-Mediated Carbon Framework with Spontaneous Metal Assembly for Structure-Tunable Metal/Carbon Nanofibers.

Vapor phase carbon (C)-reduction-based syntheses of C nanotubes and graphene, which are highly functional solid C nanomaterials, have received extensive attention in the field of materials science. This study suggests a revolutionary method for precisely controlling the C structures by oxidizing solid C nanomaterials into gaseous products in the opposite manner of the conventional approach. This gaseous nanocarving enables the modulation of inherent metal assembly in metal/C hybrid nanomaterials because of the promoted C oxidation at the metal/C interface, which produces inner pores inside C nanomaterials. This phenomenon is revealed by investigating the aspects of structure formation with selective C oxidation in the metal/C nanofibers, and density functional theory calculation. Interestingly, the tendency of C oxidation and calculated oxygen binding energy at the metal surface plane is coincident with the order Co > Ni > Cu > Pt. The customizable control of the structural factors of metal/C nanomaterials through thermodynamic-calculation-derived processing parameters is reported for the first time in this work. This approach can open a new class of gas-solid reaction-based synthetic routes that dramatically broaden the structure-design range of metal/C hybrid nanomaterials. It represents an advancement toward overcoming the limitations of intrinsic activities in various applications.

Controlled Molybdenum Disulfide Assembly inside Carbon Nanofiber by Boudouard Reaction Inspired Selective Carbon Oxidation.

Vertical stacking and lateral growth of molybdenum disulfide (MoS2 ) are controlled with remarkable precision, and MoS2 nanotubes are directly converted from nanofibers. Predictive synthesis is enabled by identifying the specific thermodynamic region where the Boudouard reaction becomes favored. It reveals how the chemical potential of each species in the MoSCO system can predict phase behaviors.