Rapid communications in mass spectrometry : RCM
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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.
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Rapid Commun. Mass Spectrom. · Jan 1998
Clinical TrialHigh-performance liquid chromatography tandem mass spectrometry procedure with automated solid phase extraction sample preparation for the quantitative determination of paclitaxel (Taxol) in human plasma.
A sensitive, specific, accurate and reproducible analytical method was developed and validated for the quantitation of the anticancer agent paclitaxel in human plasma. This procedure is based on high performance liquid chromatography/ion spray-tandem mass spectrometry. This methodology is highly specific because a MS/MS technique (multiple reactant-ion monitoring, MRM) was used for both paclitaxel and its internal standard. ⋯ The intra and inter-day precision were within 12%, and accuracy was included in the range 102-110%. Paclitaxel recovery assessed at 15,250 and 500 ng/mL, was determined to be greater than 85%. The assay is applicable to clinical pharmacokinetic studies.
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Rapid Commun. Mass Spectrom. · Jan 1996
ReviewThe novel selected-ion flow tube approach to trace gas analysis of air and breath.
We present an overview of the development and use of our selected-ion flow tube (SIFT) technique as a sensitive, quantitative method for the rapid, real-time analysis of the trace gas content of atmospheric air and human breath, presenting some pilot data from various research areas in which this method will find valuable application. We show that it is capable of detecting and quantifying trace gases, in complex mixtures such as breath, which are present at partial pressures down to about 10 parts per billion. Following discussions of the principles involved in this SIFT method of analysis, of the experiments which we have carried out to establish its quantitative validity, and of the air and breath sampling techniques involved, we present sample data on the detection and quantification of trace gases on the breath of healthy people and of patients suffering from renal failure and diabetes. ⋯ Throughout the paper we stress the advantages of this SIFT method compared to conventional mass spectrometry for trace gas analysis of complex mixtures, emphasizing its selectivity, sensitivity and real-time analysis capability. Finally, we note that whilst the current SIFT is strictly laboratory based, both transportable and portable instruments are under construction and development. These instruments will surely extend the application of this analytical technique into more areas and allow greater exploitation of their on-line and real-time features.