Biomedical subjects

Chung-Ping Yu

Publications and source records attributed to Chung-Ping Yu.

4 recordsLinked to original sources

PubMed2006

Incorporation of a nanosplitter interface into an LC-MS-RD system to facilitate drug metabolism studies.

In the work reported here, a novel interface, the nanosplitter, is incorporated into the drug metabolism laboratory in order to enhance the analytical capabilities of detecting and identifying drug-related metabolites to support drug metabolism studies during the drug development process. When an existing LC-MS-radiometric detector (RD) system is coupled with this nanosplitter, the system becomes capable of performing dynamic microspray under a typical analytical LC method. With the superior MS sensitivity offered by this system, most of the analytical LC methods developed for metabolite profiling can then be easily adopted for metabolite identification work. The improvement of these analytical capabilities can streamline the entire process of the drug metabolism study. In the experiments presented here, the nanosplitter interface coupled with analytical HPLC systems (e.g. 4.6 x 250 mm column @ 1 ml/min) demonstrated significant increases in MS signal (2x to 40x peak area) when compared to the standard LC-MS interface for both in vitro and in vivo metabolism studies. Furthermore, this signal gain facilitated the MS detection of additional metabolites (observed in the radiometric trace) that were below the MS level of detection when using the standard interface.

Animals↗

PubMed2005

Cyanide trapping of iminium ion reactive intermediates followed by detection and structure identification using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Secondary and tertiary alicyclic amines are widely found in pharmaceuticals and environmental compounds. The formation of iminium ions as reactive intermediates in the metabolic activation of alicyclic amines has previously been investigated in radiometric assays where radiolabeled cyanide is typically employed. In this paper, we report a relatively high throughput LC-MS/MS method for the detection of the nonradiolabeled cyanide adduct formed in rat or human liver microsomal incubations via constant neutral loss scan followed by structural characterization using product ion scan on a triple quadrupole mass spectrometer. A total of 14 alicyclic amine compounds were investigated with the cyanide trapping LC-MS/MS screen and also with the glutathione (GSH) trapping screen, a well-established and commonly employed technique for reactive metabolite screening. Our results are found to be in general agreement with the previous metabolism reports for these compounds, demonstrating the effectiveness, speed, and simplicity of the cyanide trapping LC-MS/MS method to study the iminium ion intermediates from alicyclic amines and its complementarities to GSH trapping method for reactive metabolite screenings.

Amines↗

PubMed2004

Improved liquid chromatography-mass spectrometry performance in quantitative analysis using a nanosplitter interface.

Several pairs of analytes in plasma were investigated to demonstrate the successful utility of a novel interface in quantitative bioanalytical LC-MS and LC-MS/MS. Recently in our laboratory, an interface (the nanosplitter) was developed that allows the coupling of normal-bore liquid chromatography with microelectrospray mass spectrometry. The post-column concentric split minimizes turbulence and is shown to produce significant gains in the mass spectrometric signal. This configuration of the splitter allows sampling of the center portion of the parabolic HPLC plug, which maintains chromatographic integrity while producing high split ratios and effectively conserving nearly 99.9% of the sample. When utilizing a Finnigan mass spectrometer (with a heated capillary interface design), the signal gain with the nanosplitter ranged from 5 to 16 times the peak area obtained using the conventional interface without splitting. The linearity of the nanosplitter and conventional interface are shown to be comparable for all analytes tested. The nanosplitter was also fitted to a Sciex mass spectrometer and the results were compared to those from turbo ionspray. While in this case no significant signal improvement was observed, when normalized to the actual analyte mass introduced into the MS, the mass sensitivity was still increased 270-fold. The variations in signal gain utilizing the nanosplitter on instruments from different manufacturers reflect the inherent differences in the source designs while confirming the benefits of coupling high flow LC separations with low flow mass spectrometric detection.

Chromatography, Liquid↗

PubMed2004

Pleomorphic xanthoastrocytoma: report of two cases and review of the prognostic factors.

Pleomorphic xanthoastrocytoma (PXA) is a superficially located, rare glial tumour first described in 1979. It affects young patients, who often present with seizures. The tumour has a relatively favourable prognosis, but 15-20% progress to malignancy. We describe two cases of PXA, both with benign features at presentation, one of which underwent anaplastic transformation. Surgery remains the mainstay of treatment. Factors influencing clinical outcome include extent of resection, and histological features such as mitotic index, necrosis and lymphocytic infiltration. The roles of radiotherapy and chemotherapy remain undefined. We advocate lifelong follow-up and establishment of a central registry in order to further the understanding of this infrequently encountered tumour.

Adult↗