Rapid communications in mass spectrometry : RCM
-
Rapid Commun. Mass Spectrom. · Jan 1999
The use of capillary high performance liquid chromatography with electrospray mass spectrometry for the analysis of small volume blood samples from serially bled mice to determine the pharmacokinetics of early discovery compounds.
The methodology described demonstrates, for the first time, the feasibility of performing pharmacokinetic studies in the serially bled mouse model to support the early development of discovery compounds. Sample analysis, using capillary high performance liquid chromatography combined with tandem mass spectrometry, has facilitated the achievement of this milestone and has successfully been applied to determine pharmacokinetic information following both intravenous and oral administration of a single discovery compound. The methodologies described demonstrate potential for a reduction in the amount of new chemical entity required to undertake pharmacokinetic studies. ⋯ The use of capillary high performance liquid chromatography (HPLC) has facilitated the analysis of small volume blood samples by increasing the effective sensitivity of the analytical method. Consequently, we have established a protocol for serially bleeding mice thus reducing the number of animals and so further reducing the amount of compound required for such experiments. This paper reports data obtained from collected and processed blood volumes of <20 microL with the subsequent injection of only 1 microL of precipitated extract onto a capillary column.
-
Rapid Commun. Mass Spectrom. · Jan 1999
Quantification of breath isoprene using the selected ion flow tube mass spectrometric analytical method.
We have used our selected ion flow tube mass spectrometric method (SIFT-MS) to study isoprene levels in the alveolar breath of 29 healthy volunteers during normal working hours at the varying states of nutrition occurring during this period. Quantification of the breath isoprene was achieved using O(2)(+) precursor ions to avoid complications which can arise when using H(3)O(+) precursor ions for isoprene analysis. ⋯ These levels are compared with those previously determined using other techniques and are seen to be at the low end of the values previously reported. The present studies are a prelude to an investigation of the proposed correlation of breath isoprene levels with psychological, physical and biochemical stress.