ABSTRACT
OBJECTIVE To establish a method for simultaneous determination of atorvastatin （ATV） and its active metabolites 2-hydroxy atorvastatin acid （2-HAT）， 4-hydroxy atorvastatin acid （4-HAT） and toxic metabolite atorvastatin lactone （ALT） in rat plasma and apply it for pharmacokinetic study. METHODS LC-MS/MS method was adopted for analysis. The one-step precipitation method was used for processing plasma samples （plasma samples were pretreated by acidification to adjust pH value so as to prevent inversion of configuration）， gradient elution was used to analyze the samples， and the analysis time was 5 min. Electrospray positive ionization was adopted， and positive ion scanning was performed in multi-reaction monitoring. The m/z of quantified ion pairs of ATV and its metabolites such as 2-HAT， 4-HAT and ATL， and internal standard pitavastatin were 559.3→ 440.2， 575.2→440.3， 575.0→440.2， 540.9→448.2 and 422.2→290.0， respectively. After conducting a comprehensive methodological investigation of the analytical method， the concentrations of ATV and its metabolites 2-HAT， 4-HAT，and ATL were determined， and the pharmacokinetic parameters of ATV and its metabolites were calculated using the non- compartment model of WinNonlin 6.1. RESULTS The results of methodological validation showed that endogenous substances in blank plasma did not interfere with the determination of the components to be tested， and the standard curve had a good linear relationship； the lower limits of quantification for ATV， 2-HAT， 4-HAT and ATL were 0.5， 0.5， 0.25 and 0.063 nmol/L， respectively. The precision， accuracy， recovery， matrix effect and stability investigation were all in line with the requirements of biological analysis. Pharmacokinetic analysis showed that after intragastric administration in rats， ATV calcium metabolized rapidly， and was mainly exposed to blood circulation in the form of ATV and 2-HAT， with the lowest concentration of lactone-type metabolites. CONCLUSIONS The established method is precise， rapid and accurate for plasma concentration analysis of ATV and its active/toxic metabolites. The application of the method could help to fully elucidate the pharmacokinetic characteristics of atorvastatin calcium in rats.
ABSTRACT
Objective To evaluate the feasibility of utilizing dose-volume histogram (DVH) prediction models of organs at risk (OARs) to deliver automatic treatment planning of prostate cancer.Methods The training set included 30 cases randomly selected from a database of 42 cases of prostate cancer receiving treatment planning.The bladder and rectum were divided into sub-volumes (Ai) of 3 mm in layer thickness according to the spatial distance from the boundary of planning target volume (PTV).A skewed normal Gaussian function was adopted to fit the differential DVH of Ai,and a precise mathematical model was built after optimization.Using the embedded C++ subroutine of Pinnacle scripa,ahe volume of each Ai of the remaining validation set for 12 patients was obtained to predict the DVH parameters of these OARa,ahich were used as the objective functions to create personalized Pinnacle script.Finalla,automatic plans were generated using the script.The dosimetric differences among the original clinical plannina,aredicted value and the automatic treatment planning were statistically compared with paired t-test.Results DVH residual analysis demonstrated that predictive volume fraction of the bladder and rectum above 6 000 cGy were lower than those of the original clinical planning.The automatic treatment planning significantly reduced the V70,V60,V50 of the bladder and the V70 and V60 of the rectum than the original clinical planning (all P＜0.05),the coverage and conformal index (CI) of PTV remained unchangea,and the homogeneity index (HI) was slightly decreased with no statistical significance (P＞ 0.05).Conclusion The automatic treatment planning of the prostate cancer based on the DVH prediction models can reduce the irradiation dose of OARs and improve the treatment planning efficiency.
ABSTRACT
Gas chromatography with mass spectrum detector ( GC-MSD) coupled with purge-and-trap system was set up to analyze the concentration of isoprene in natural waters. The best experimental conditions were established, including purge gas flow rate ( 50 mL/min ) , purge time ( 15 min ) , the optimum capillary column ( Rt-Alumina BOND/KCl) and the appropriate condition of temperature programming. When analyzing isoprene in natural waters, the precision was <4% (n=6), the detection limit was 0. 5 pmol/L and the recovery was 91%-102%. The preservative experiment showed that there was no obvious variation in sample concentrations of isoprene within 60 days. The concentrations of isoprene measured with the method ranged from 60 . 8 to 278 . 7 pmol/L in the Jiaozhou Bay and its adjacent river estuaries and from 44 . 7 to 77 . 2 pmol/L in Yellow River estuary, which was in good accord with those results reported in literatures in other coastal waters. In conclusion, the analytical method could meet the requirements of the analysis of concentration of isoprene in natural waters.