Cross-platform Q-TOF validation of global exo-metabolomic analysis: application to human glioblastoma cells treated with the standard PI 3-Kinase inhibitor LY294002.

The reproducibility of a metabolomics method has been assessed to identify changes in tumour cell metabolites. Tissue culture media extracts were analyzed by reverse phase chromatography on a Waters Acquity T3 column with a 13 min 0.1% formic acid: acetonitrile gradient on Agilent and Waters LC-Q-TOF instruments. Features (m/z, RT) were extracted by MarkerLynx (Waters) and Molecular Feature Extractor (Agilent) in positive and negative ionization modes. The number of features were similar on both instruments and the reproducibility of ten replicates was <35% signal variability for approximately 50% and 40% of all ions detected in positive and negative ionization modes, respectively. External standards spiked to the matrix showed CVs <25% in peak areas within and between days. U87MG glioblastoma cells exposed to the PI 3-Kinase inhibitor LY294002 showed significant alterations of several confirmed features. These included glycerophosphocholine, already shown by NMR to be modulated by LY294002, highlighting the power of this technology for biomarker discovery.

Site-selective hole burning in Eu3+:Y2SiO5.

We found that the Eu3+ ion occupies several distinct sites in Y2SiO5. We were also able to perform hole-burning studies in more than 40 different transitions.

Utilization of salivary concentrations of ciprofloxacin in subjects with cystic fibrosis.

Ciprofloxacin, an orally-absorbed fluoroquinolone is effective against multiply resistant Pseudomonas aeruginosa in cystic fibrosis patients. It is the only practicable agent against extraintestinal salmonellosis and shigellosis in developing countries. However, concern with the risk of arthropathy in young children has restricted its use in pediatrics. Pharmacokinetic studies with ciprofloxacin are limited in the pediatric population. As a result, the dose and frequency of administration are not established in children. In this study the possibility of using salivary concentrations as surrogate measure of serum concentrations was investigated. A pediatric formulation of the drug (125 mg per capsule) was prepared and compared to 250 mg tablets. Relative bioavailability was 105% (tablet/capsule). The time to peak salivary concentration and elimination rate from saliva were significantly different from serum (p < 0.01 and p < 0.05 respectively). The linear regression analysis of post-peak concentrations in serum and saliva yielded a slope of 1.25 and correlation coefficient of 0.83. It was also found that salivary concentrations may be contaminated from drug retained in the oral cavity. The conclusion was drawn that salivary concentrations could not be reliably used as a surrogate measure of serum levels for therapeutic drug monitoring.