Toxicity and toxicokinetics of a phosphorothioate oligonucleotide against the c-myc oncogene in cynomolgus monkeys.

A 2-week toxicity and toxicokinetic study of a 15-mer phosphorothioate oligonucleotide, INX-3280, against the c-myc oncogene was performed in cynomolgus monkeys. As this oligonucleotide readily adopts an aggregate structure, a quadruplex, which may be associated with adverse physiologic effects, this study was performed using INX-3280 that had been converted to its monomeric form. Animals received intravenous (i.

Improved GC/MS analysis of opiates with use of oxime-TMS derivatives.

An improved gas chromatographic/mass spectrometric (GC/MS) assay is described for the quantitation of codeine and morphine as trimethylsyl (TMS) derivatives. The TMS derivatization of ketone-containing opiates results in the formation of multiple derivatives. Some of these products have retention times close to those of codeine-TMS and morphine-TMS.

Reduction in extraction efficiency of charged particles from the ion source as the cause of matrix effects in the GC-MS analysis of drugs.

Previous studies have shown that the ion response of a compound can be suppressed by the presence of a large amount of a coeluting substance in a gas chromatographic-mass spectrometric (GC-MS) system. In the present study, the change in the ion current of a constant amount of diazepam-d5 in the presence of a 100-fold amount of diazepam was used to monitor this condition in the Hewlett Packard mass selective detector (MSD). It was observed that a reduced recovery of ions occurred when the potentials of the MSD source elements were established by the autotune algorithm.

Characterization of drug interferences caused by coelution of substances in gas chromatography/mass spectrometry confirmation of targeted drugs in full-scan and selected-ion monitoring modes.

Interference by substances coeluting with targeted drugs is a general problem for gas chromatographic/mass spectrometric analysis of urine. To characterize these interferences, we examined human urine samples containing benzoylecgonine and fluconazole, and other drug combinations including deuterated internal standards that coelute (ISd,c) with target drugs, by selected-ion monitoring (SIM) and full-scan mass spectrometry. We show that, by SIM analysis, detecting the presence of an interferent is dependent on the specific IS used for the assay.