Comparison of a 250 kV single-stage accelerator mass spectrometer with a 5 MV tandem accelerator mass spectrometer--fitness for purpose in bioanalysis.

The introduction of 'compact' accelerator mass spectrometers into biomedical science, including use in drug metabolism and bioanalytical applications, is an exciting recent development. Comparisons are presented here between a more established and relatively large tandem accelerator which operates at up to 5 MV and a conventional laboratory-sized 250 kV single-stage accelerator mass spectrometer. Biological samples were enriched with low levels of radiocarbon, then converted into graphite prior to analysis on each of the two instruments.

GW274150, a novel and highly selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), shows analgesic effects in rat models of inflammatory and neuropathic pain.

Nitric oxide (NO), synthesised by different isoforms of nitric oxide synthase (NOS), has been linked with the development and maintenance of nociception. We studied the role of the inducible isoform, iNOS, in two different rat pain models with an inflammatory component. iNOS was immunohistochemically detected locally in the paw 6h after Freund's Complete Adjuvant (FCA) injection, showing a plateau at 24-72 h and falling slowly in the following weeks.

Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans.

Ondansetron is cleared primarily by metabolism in humans, with hydroxylation of the indole moiety in the 7- and 8-positions being the major identified phase I pathways. In vitro studies using lymphoblastoid cell lines expressing single human cytochrome P450 forms and hepatic microsomes were undertaken to investigate the forms involved in the metabolism of ondansetron in humans. The cell lines that expressed CYP1A1, CYP1A2, and CYP2D6 were shown to be capable of metabolizing [14C]ondansetron.

Disposition of salmeterol xinafoate in laboratory animals and humans.

The disposition of [14C]salmeterol xinafoate, a new inhaled beta 2-adrenoceptor agonist with both bronchodilator and antiinflammatory activity, has been studied in laboratory animals and humans following intravenous and oral administration. [14C]Salmeterol was rapidly absorbed in animal species and humans with Cmax observed within 2 hr. Cmax was similar for normalized oral dose level in mice, rats, and rabbits.

Determination of salmeterol in rat and dog plasma by high-performance liquid chromatography with fluorescence detection.

Salmeterol (as the hydroxynaphthoate) is the first of a new class of long-acting beta-adrenergic receptor agonists with both bronchodilator and anti-inflammatory actions. A sensitive, accurate, and precise high-performance liquid chromatographic method for the determination of salmeterol in rat and dog plasma is described. Samples are prepared by solid-phase extraction and, after chromatography of the extracts on a reversed-phase styrene/divinylbenzene analytical column, salmeterol is detected by fluorescence monitoring (excitation wavelength, 230 nm; emission wavelength, 305 nm).