Biomedical subjects

Jiwen Chen

Publications and source records attributed to Jiwen Chen.

9 recordsLinked to original sources

PubMed2006

Mapping pharmaceuticals in tissues using MALDI imaging mass spectrometry.

During drug discovery and development stage, often the question is raised as to whether the drug can reach the site of action which helps researchers better assess the potential value of that compound as a pharmaceutical product and toxicological outcomes. High performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS) has totally replaced HPLC methods that use UV or other detectors for most drug analysis applications. However, HPLC-MS/MS approaches are not able to provide the answer to certain questions regarding the distribution of a drug in various organs or tissues from laboratory animal experiments. Whole body radioautography (WBA) normally provides a standard means to answer this question on the time course of the drug candidates. However, the major disadvantage in this radioautographic technique is to allow for visualization of total drug-related materials but to image the distribution of the administrated drugs and their metabolites in all tissues. In addition, the availability of radiolabeled compounds at drug discovery stage is another concern. To overcome these issues, matrix-assisted laser desorption/ionization-mass spectrometric method (MALDI-MS) has been developed to directly determine the distribution of pharmaceuticals in tissue sections which might unravel their disposition or biotransformation pathway for new drug development.

Animals↗

PubMed2006

Supercritical fluid chromatography-tandem mass spectrometry for the enantioselective determination of propranolol and pindolol in mouse blood by serial sampling.

Packed-column supercritical fluid chromatography (pSFC) coupled to an atmospheric pressure chemical ionization (APCI) source and a tandem mass spectrometer (MS/MS) with minimum sample pretreatment was explored for the rapid and enantioselective determination of (R,S)-propranolol in mouse blood. Serial bleeding of mice is advantageous for the reduction of animal usage, dosing errors, and animal-to-animal variation. The effects of the eluent flow rate and composition as well as the nebulizer temperatures on the ionization efficiency of racemic propranolol and pindolol as model compounds in the positive ion mode under pSFC conditions were studied. The fundamental parameters on the proposed hyphenated system such as matrix ionization suppression and chromatographic performances were investigated in improving sensitivity and enantiomeric separation for the detection of the analytes. The proposed chiral pSFC-APCI/MS/MS approach requiring approximately 3 min/sample for the determination of (R,S)-propranolol at a low nanogram per milliliter region was partially validated with respect to specificity, linearity, reproducibility, and accuracy and was applied to support a pharmacokinetic study.

Adrenergic beta-Antagonists↗

PubMed2006

Investigation of the profiling depth in matrix-assisted laser desorption/ionization imaging mass spectrometry.

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry is generally considered to be a surface analysis technique. In this report, the profiling depth of imaging mass spectrometry was examined. MALDI matrix solution was found to be able to gain access to the tissue interior and extract analyte molecules to the tissue surface. As a consequence, prazosin, a small molecule pharmaceutical compound, located as deep as 40 microm away from the surface was readily detected after matrix application. Likewise, cytochrome c, a 12 kDa protein, was also detectable from the tissue interior. Moreover, for prazosin, not only the extent of matrix effect, but also the extraction efficiency of the matrix solvent appeared to be dependent on the type of tissue. These results indicated that experimental conditions that decrease the matrix solvent evaporation during matrix application may increase analyte extraction efficiency and hence sensitivity of the analysis. Furthermore, thin sections should be used to avoid differential extraction efficiency of matrix solvent in different tissues for whole-body analysis.

Animals↗

PubMed2006

Matrix-assisted laser desorption/ionization imaging mass spectrometry for direct measurement of clozapine in rat brain tissue.

Matrix-assisted laser desorption/ionization hyphenated with quadrupole time-of-flight (QTOF) mass spectrometry (MS) has been used to directly determine the distribution of pharmaceuticals in rat brain tissue slices which might unravel their disposition for new drug development. Clozapine, an antipsychotic drug, and norclozapine were used as model compounds to investigate fundamental parameters such as matrix and solvent effects and irradiance dependence on MALDI intensity but also to address the issues with direct tissue imaging MS technique such as (1) uniform coating by the matrix, (2) linearity of MALDI signals, and (3) redistribution of surface analytes. The tissue sections were coated with various matrices on MALDI plates by airspray deposition prior to MS detection. MALDI signals of analytes were detected by monitoring the dissociation of the individual protonated molecules to their predominant MS/MS product ions. The matrices were chosen for tissue applications based on their ability to form a homogeneous coating of dense crystals and to yield greater sensitivity. Images revealing the spatial localization in tissue sections using MALDI-QTOF following a direct infusion of (3)H-clozapine into rat brain were found to be in good correlation with those using a radioautographic approach. The density of clozapine and its major metabolites from whole brain homogenates was further confirmed using fast high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) procedures.

Animals↗

PubMed2005

Chiral liquid chromatography-tandem mass spectrometric methods for stereoisomeric pharmaceutical determinations.

The characterization of the drug metabolism and pharmacokinetic (DMPK) profiles of stereoisomers is a fundamental aspect of the drug discovery and development processes. Therefore, chiral drug bioassays are very important to pharmaceutical and biomedical researchers. The recent developments in chiral liquid chromatography coupled to atmospheric pressure ionization tandem mass spectrometry (LC-API-MS/MS) for the analysis of pharmaceuticals are reviewed. Various ionization techniques including electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric photoionization (APPI) interfaced with chiral liquid chromatographic methods are described in terms of their ionization efficiencies, matrix effects and limitations. Examples were selected to demonstrate the applicability of these methods for enantioselective bioanalysis.

Chromatography, High Pressure Liquid↗

PubMed2005

Chiral supercritical fluid chromatography/tandem mass spectrometry for the simultaneous determination of pindolol and propranolol in metabolic stability samples.

A chiral packed-column supercritical fluid chromatographic (pSFC) system coupled to tandem mass spectrometer (MS/MS) for the rapid measurements of (R,S)-propranolol and (+/-)-pindolol in metabolic stability samples was developed. The effects of the eluent flow rates and compositions, as well as of the nebulizer temperature, on the chromatographic performance and the ionization efficiency of the analytes in positive ion mode under pSFC conditions were studied. The ionization mechanism of the analytes in the CO2/methanol atmospheric pressure chemical ionization (APCI) environments with or without the use of an additive was studied. The chiral pSFC-APCI-MS/MS approach requiring approximately 2 min per sample was applied for the simultaneous determination of two pairs of racemic drugs in in vitro samples at low nanogram per milliliter concentrations.

Animals↗

PubMed2005

Simultaneous determination of nicotinic acid and its metabolites using hydrophilic interaction chromatography with tandem mass spectrometry.

A hydrophilic interaction chromatographic (HILIC) system interfaced with atmospheric pressure ionization (API) sources and a tandem mass spectrometer (MS/MS) was developed for the simultaneous determination of nicotinic acid (NiAc) and its metabolites in dog plasma in support of a pharmacokinetic study. A silica column was adapted for separation of NiAc and its two metabolites, nicotinamide (NiNH2) and nicotinuric acid (NiUAc), under HILIC conditions. The influence of experimental factors such as the composition of mobile phase on ionization efficiency and chromatographic performance of all analytes was investigated. The feasibility of the proposed HILIC/MS/MS methods was explored by comparing the plasma levels of NiAc, NiNH2, and NiUAc in dog obtained by using either electrospray ionization or atmospheric pressure chemical ionization interfaces in positive ion mode. The methods were partially validated in terms of inter-day accuracy and precision, extraction recovery, benchtop and freeze/thaw stability. Further, the potential of ionization suppression resulting from endogenous components of the biological matrixes on the HILIC/API-MS/MS methods were investigated using the post-column infusion technique.

Animals↗

PubMed2005

Stabilizing drug molecules in biological samples.

Stability is one of the basic parameters, along with accuracy, precision, selectivity, and sensitivity, for bioanalytic method validation in nonhuman and clinical pharmacology/toxicology, bioavailability (BA), bioequivalence (BE), and other studies related to the drug approval process. In the drug development stage where stability evaluation is obligatory, instability of drug candidates in biologic samples will seriously complicate assay validation. In this article, we review the general strategies and methodologies such as temperature adjustment, pH control, derivatization, and addition of inhibitors and oxidant that are commonly employed to stabilize pharmaceuticals that might be unstable in biologic samples.

Animals↗

PubMed2004

Determination of SCH 211803 by nanoelectrospray infusion mass spectrometry: evaluation of matrix effect and comparison with liquid chromatography-tandem mass spectrometry.

A high throughput assay for SCH 211803, an M2 muscarinic receptor antagonist in human plasma using nanoelectrospray infusion tandem mass spectrometry is described. Sample processing consisted of protein precipitation followed by solid phase extraction using octadecasilyl resin-filled pipette tips on a liquid handling robotic system. The sample extracts were infused directly to the mass spectrometer using a nanoelectrospray interface in a silicon chip format. SCH 211803 was quantified in plasma over the concentration range of 1-1000 ng/mL. In comparison with a liquid chromatography-tandem mass spectrometry assay, the nanoelectrospray method has comparable accuracy, precision and limit of quantitation, with a nine-fold improvement in sample throughput. Using the nanoelectrospray assay, ion suppression was evaluated and found to be 15%. This represented a four-fold reduction in matrix suppression when compared to a conventional electrospray source operating in the flow injection analysis mode at a flow rate common for LC-MS/MS analysis.

Animals↗