Fast and sensitive liquid chromatography/electrospray mass spectrometry method to study ocular penetration of EDL‐155, a novel antitumor agent for retinoblastoma in rats

Our group has used the tetrahydroisoquinoline derivative EDL‐155 to treat glioblastoma in animal models and it is currently being evaluated in the treatment of ocular cancers. The purpose of this study was to develop a rapid and sensitive liquid chromatography and tandem mass spectrometry (LC‐MS/MS) method to study the plasma and vitreous humor disposition of EDL‐155 in rats. Animals received a single periocular injection of EDL‐155 (20 mg/kg). Animals were sacrificed at specified times (5, 60, 120, 240 and 360 min) and plasma and vitreous humor samples were obtained. EDL‐155 was isolated by protein precipitation and the extracts were analyzed by reversed‐phase high‐pressure liquid chromatography (HPLC) with MS/MS detection. A structurally similar analog was used as internal standard (IS). The chromatographic run time was 3.5 min per injection. The mass spectrometer was operated in positive‐ion, multiple reaction monitoring (MRM) mode. The mass transitions monitored were m/z332.2 → 167.2 (EDL‐155) and m/z391.2 → 200.2 (IS). The lower limit of quantification (LLOQ) was 0.1 ng/ml in both vitreous humor and plasma. The method was validated for selectivity, linearity, accuracy and precision in rat vitreous humor and partially validated for accuracy and precision in rat plasma. The ion suppression, recovery and stability of the analyte in the biological matrix were also tested. The assay was rapid, sensitive and robust enough to support EDL‐155 ocular penetration studies in a rodent model of intraocular cancer. Application of this method revealed that EDL‐155 was rapidly passed into the vitreous humor following periocular administration. Further, vitreous humor exposure exceeded systemic exposure by approximately sevenfold. High local concentrations coupled with minimal systemic exposure supports further testing of EDL‐155 as localized therapy for intraocular cancers. Copyright © 2009 John Wiley & Sons, Ltd.     

Quantitative determination of ginsenoside Rh2 in rat biosamples by liquid chromatography electrospray ionization mass spectrometry

Ginsenoside Rh₂ is a “hot” natural compound with great potential as a new anti-cancer drug based on abundant pharmacological experiments. However, no systemic pharmacokinetic study of Rh₂ was reported because current analysis methods could not fully meet the requirements. Thus, we developed a simple LC/MS method with highly improved sensitivities for the determination of Rh₂ in rat plasma, bile, urine, feces and most tissues. The tissues and feces were firstly homogenized mechanically using buffer and methanol as the media, respectively. Plasma, bile, urine and tissue homogenates were extracted with diethyl ether for sample preparation. Feces homogenates were directly deproteinized with acetonitrile. The subsequent analysis procedures were performed on a Shimadzu LCMS2010A system (electrospray ionization single quadrupole mass analyzer), with an ODS column (150 mm × 2.0-mm i.d., 5 μm) plus a C18 guard column for separation and ammonium chloride (500 μmol) as mobile phase additive. The proportions of mobile phase were changed timely according to gradient programs. Chlorinated adducts of molecular ions [M + Cl]⁻ of Rh₂ at m/z 657.35 and internal standard digitoxin at m/z 799.55 were monitored in selective ion monitoring mode of negative ions. The method was validated to be accurate, precise and rugged with good linearity in all matrices, according to the FDA guidelines. The lower limits of quantitation in rat plasma, urine and feces were 0.2, 0.2 and 20 ng/mL respectively. Stability studies were also performed, indicating that there were no stability-related problems in the analytical procedure of Rh₂. The proposed method was successfully applied to the preclinical pharmacokinetic research of Rh₂ in rats, including plasma kinetics, tissue distribution and excretion studies.     

Silica spheres coated with C18‐modified gold nanoparticles for capillary LC and pressurized CEC separations

Nonporous monodispersed silica spheres of 1.3 μm were coated with gold nanoparticles (AuNPs) and subsequently coated with n‐octadecanethiol. By transmission electron microscopy analysis, the average diameter of the AuNPs on the silica spheres was determined to be 12 nm. The chromatographic and electrochromatographic properties of self‐assembled n‐octadecanethiol AuNP‐coated silica microspheres (C18‐AuNPs‐SiO₂) were investigated using a group of nonpolar PAHs. The stationary phase appears to display a characteristic reversed‐phase behavior. Higher separation efficiency and shorter separation times were obtained using pressurized CEC (pCEC) compared with capillary LC (CLC). A maximum column efficiency of about 2.5×10⁵ plates per meter and less than 18 min separation time for benzene were obtained in pCEC while only 66 507 plates per meter and an analysis time of nearly 100 min were observed in CLC mode. A chemical stability test of the C18‐AuNPs‐SiO₂ stationary phase under extremely high and low pH conditions demonstrated that it is stable at pH 12 and 1 for at least 60 h. The results confirm that C18‐AuNPs‐SiO₂ possesses a high rigidity to withstand high packing pressures and can be used as a good stationary phase for CLC and pCEC.     

Further investigations of the effect of pressure on retention in ultra-high-pressure liquid chromatography

In this study, we investigated further the large increases in retention with pressure that we observed previously in RP-LC especially for ionised solutes. These findings were initially confirmed on a conventional silica C₁₈ column, which gave extremely similar results to the hybrid C₁₈ phase originally used. Large increases in retention factor of ∼50% for a pressure increase of 500 bar were also shown for high MW polar but neutral solutes. However, experiments with the same bases in ionised and non-ionised forms suggest that somewhat greater pressure-induced retention increases are found for ionised solutes. Retention increases with pressure were found to be considerably smaller for a C₁ column compared with a C₁₈ column; decreases in retention with increasing pressure were noted for ionised bases when using a bare silica column in the hydrophilic interaction chromatography (HILIC) mode. These observations are consistent with the partial loss of the solvation layer in RP-LC as the solute is forced into the hydrophobic environment of the stationary phase, and consequent reduction in the solute molar volume, while the water layer on the surface of a HILIC packing increases the hydration of a basic analyte. Finally, retention changes with pressure in RP-LC can also be observed at a mobile phase pH close to the solute pK_a, due to changes in pK_a with pressure. However, this effect has no influence on the results of most of our studies.     

存在自旋轨道耦合的介观小环中的持续自旋流

文章作者研究了存在自旋轨道耦合的介观小环的平衡态性质.此前人们已经知道,在有磁通穿过的介观小环中,绕环运动的电子会产生一附加的Berry相位而导致持续电流;同样地,在仅有自旋轨道耦合的体系中,电子绕环运动也应当会产生附加的自旋Berry相位,进而驱动持续自旋流.文章作者通过对一个有正常区和自旋轨道耦合区的复合小环的计算,结果表明,无电流伴随的纯持续自旋流的确存在.文章作者指出,这持续自旋流描述真实的自旋运动,并且它能被实验观测.     

Simultaneous determination of eight adulterants in weight management supplements and herbs by HPLC–DAD and LC–MS/MS

An efficient HPLC–DAD method was developed for simultaneous determination of eight adulterants in weight management supplements and herbs. The eight adulterants were phenolphthalein, sibutramine, nuciferine, and five anthraquinone compounds including aloe-emodin, rhein, emodin, chrysophanol, and physcion. The analytes were ultrasonically extracted with 70% (v/v) methanol aqueous solution followed by centrifugation. The supernatant was subjected to HPLC analysis. A Phenomenex Luna C18 column was applied for chromatographic separation. The mobile phase was consisted of methanol and aqueous solution of 0.05% (v/v) phosphoric acid–0.025% (m/v) sodium dodecyl sulfonate. The flow rate of mobile phase was 0.8?ml?min^?1 with gradient elution. Clenbuterol and ibuprofen were used as internal standards. The retention times and the characteristic UV spectrograms were used for qualitative analysis. Quantifications were based on the internal standard curves. Good linearities (r?>?0.9996) for all analytes were obtained with the intra- and inter-day precision (n?=?6) ranging from 0.76 to 5.9% and 0.90 to 8.1%, respectively. The average recoveries from the spiked samples with different matrices varied from 73.4 to 114%. Validations were subsequently performed using LC–MS/MS. The proposed method successfully determined the target adulterants in eight commercial weight management supplements and five weight reducing herbs with satisfactory results.     

Self‐Propelled Polymer Nanomotors

Polymer conformations: The picture shows instantaneous conformations of product molecules produced in a catalytic reaction at the head of a polymer chain. The extended (left) and collapsed (right) polymers correspond to chains in good and poor solvent conditions, respectively. The product molecule concentration gradient leads to a directed force on the polymer, so that it functions as a self‐propelled nanomotor.

     

Factors affecting the reversed-phase liquid chromatographic separation of polycyclic aromatic hydrocarbon isomers

Reversed-phase liquid chromatography (LC) on C₁₈ stationary phases provides excellent selectivity for the separation of polycyclic aromatic hydrocarbons (PAH). Recent studies have shown that several factors affect selectivity for the LC separation of PAH including phase type (monomeric or polymeric), pore diameter and surface area of the silica substrate, and surface density of the C₁₈ ligands. In this paper the separation of eleven PAH isomers of molecular weight 278 is used to further illustrate the effect of stationary phase characteristics and shape of the solute (length-to-breadth ratio, L/B) on retention and selectivity. Only polymeric C₁₈ phases with a high C₁₈ surface coverage provided separation of all eleven isomers and the elution order of these isomers generally followed increasing L/B values. The effect of solute nonplanarity on reversed-phase LC retention was investigated on both monomeric and polymeric phases using a series of planar and nonplanar PAH pairs. For each solute pair, the nonplanar solute eluted earlier than the planar solute, the largest selectivity factors being observed on the C₁₈ phase with the highest percent carbon load. Based on these studies, a model is proposed to describe the retention of PAH on polymeric C₁₈ phases.     

Impulsive stabilization of a class of nonlinear system with bounded gain error

Considering mechanical limitation or device restriction in practical application, this paper investigates impulsive stabilization of nonlinear systems with impulsive gain error. Compared with the existing impulsive analytical approaches,the proposed impulsive control method is more practically applicable, which includes control gain error with an acceptable boundary. A sufficient criterion for global exponential stability of an impulsive control system is derived, which relaxes the condition for precise impulsive gain efficiently. The effectiveness of the proposed method is confirmed by theoretical analysis and numerical simulation based on Chua＇s circuit.