LC–MS–MS Study of the Pharmacokinetics of a 9-β-Dihydro-9,10-O-acetal Derivative of Docetaxel in Rats and Beagle Dogs

SHR110008 is a representative 9-β-dihydro-9,10-O-acetal taxane with greater anticancer activity and less toxicity than docetaxel. To support a preclinical study of its pharmacokinetics and to predict the effect of 9-β-dihydro-9,10-O-acetal modification on its pharmacokinetic properties, we have developed a sensitive and rapid liquid chromatographic–tandem mass spectrometric method for quantitative analysis of SHR110008 in rat and dog plasma. Plasma was extracted with ethyl acetate. The analytes were separated on a 150 × 4.6 mm i.d., 5 μm particle, reversed-phase C₁₈ column with 90:10 (v/v) methanol–0.1% formic acid as mobile phase at a flow rate of 0.3 mL min⁻¹. Detection was performed by triple-quadrupole tandem mass spectrometry in selected reaction monitoring (SRM) mode with an electrospray ionization source. The precursor-to-product ion transition m/z 933 → 142 was used. The method was validated for accuracy and precision, and linearity in the two matrices was good. Lower limits of quantification (LLOQ) in rat and dog plasma were 5 and 2 ng mL⁻¹, respectively. There were no stability-related problems in the procedure for analysis of SHR110008. The method was successfully used in a preclinical study of the pharmacokinetics of SHR110008 in rats and beagle dogs. The pharmacokinetics of SHR110008 were non-linear in rats and dogs. The elimination half-life ranged from 5.18 to 7.32 h for the rats and from 6.42 to 8.42 h for the dogs.

     

Energy spectra for decaying 2D turbulence in a bounded domain

We use results derived in the framework of the replica approach to study the liquid-glass thermodynamic transition. The main results are derived without using replicas and applied to the study of the Lennard-Jones binary mixture introduced by Kob and Andersen. We find that there is a phase transition due to the entropy crisis. We compute both analytically and numerically the value of the phase transition point T(K) and the specific heat in the low temperature phase.     

LC–MS–MS Study of the Pharmacokinetics of a 9-β-Dihydro-9,10-O-acetal Derivative of Docetaxel in Rats and Beagle Dogs

SHR110008 is a representative 9-β-dihydro-9,10-O-acetal taxane with greater anticancer activity and less toxicity than docetaxel. To support a preclinical study of its pharmacokinetics and to predict the effect of 9-β-dihydro-9,10-O-acetal modification on its pharmacokinetic properties, we have developed a sensitive and rapid liquid chromatographic–tandem mass spectrometric method for quantitative analysis of SHR110008 in rat and dog plasma. Plasma was extracted with ethyl acetate. The analytes were separated on a 150 × 4.6 mm i.d., 5 μm particle, reversed-phase C₁₈ column with 90:10 (v/v) methanol–0.1% formic acid as mobile phase at a flow rate of 0.3 mL min^?1. Detection was performed by triple-quadrupole tandem mass spectrometry in selected reaction monitoring (SRM) mode with an electrospray ionization source. The precursor-to-product ion transition m/z 933 → 142 was used. The method was validated for accuracy and precision, and linearity in the two matrices was good. Lower limits of quantification (LLOQ) in rat and dog plasma were 5 and 2 ng mL^?1, respectively. There were no stability-related problems in the procedure for analysis of SHR110008. The method was successfully used in a preclinical study of the pharmacokinetics of SHR110008 in rats and beagle dogs. The pharmacokinetics of SHR110008 were non-linear in rats and dogs. The elimination half-life ranged from 5.18 to 7.32 h for the rats and from 6.42 to 8.42 h for the dogs.     

Biomolecular interaction monitoring of autoantibodies by scanning surface plasmon resonance microarray imaging

A new commercial surface plasmon resonance (SPR) imaging analysis system with a novel SPR dip angle scanning principle allows the measurement, without the need for labeling, of the exact SPR dip angle. With this system hundreds of biomolecular interactions can be monitored on microarrays simultaneously and with great precision. The potency of this system is demonstrated by automatically monitoring the interactions between citrullinated peptides and serum autoantibodies of 50 rheumatoid arthritis (RA) patients and 29 controls in a single step. The smallest antibody concentration that could be measured in this experimental setup was 0.5 pM.