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

Chen, Jiwen; Kapron, James T.; Ma, Li; Pace, Ellan; Pelt, Colleen K. Van; Rudewicz, Patrick J.

doi:10.1016/j.jchromb.2004.06.005

Cited by 13 publications

(10 citation statements)

References 15 publications

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“…Acylcarnitines and organic acids were measured using stable isotope dilution techniques as previously described (35,36). Acylcarnitine species were measured using flow injection tandem mass spectrometry (MS/MS) and sample preparation methods described previously (37,38). Organic acids were quantified using a previously described method that utilizes Trace GC Ultra coupled to a Trace DSQ MS operating under Excalibur 1.4 (Thermo Fisher Scientific) (35).…”

Section: Methodsmentioning

confidence: 99%

Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease

Dong¹,

Saha

Huang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

221

242

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Constitutive androstane receptor CAR (NR1I3) has been identified as a central mediator of coordinate responses to xenobiotic and endobiotic stress. Here we use leptin-deficient mice (ob/ob) and ob/ob, CAR ؊/؊ double mutant mice to identify a metabolic role of CAR in type 2 diabetes. Activation of CAR significantly reduces serum glucose levels and improves glucose tolerance and insulin sensitivity. Gene expression analyses and hyperinsulinemic euglycemic clamp results suggest that CAR activation ameliorates hyperglycemia by suppressing glucose production and stimulating glucose uptake and usage in the liver. In addition, CAR activation dramatically improves fatty liver by both inhibition of hepatic lipogenesis and induction of ␤-oxidation. We conclude that CAR activation improves type 2 diabetes, and that these actions of CAR suggest therapeutic approaches to the disease.insulin resistance ͉ nuclear receptor ͉ xenobiotics

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Section: Methodsmentioning

confidence: 99%

Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease

Dong¹,

Saha

Huang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

221

242

View full text Add to dashboard Cite

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“…The attempt to further increase sample throughput has led some bioanalytical laboratories to replace chromatographic separation with flow injection analysis (FIA) [42,43] or nanoelectrospray infusion techniques [44][45][46] that eliminate the HPLC component. In addition to a higher-throughput potential, the "columnless" MS-based methods such as nanoelectrospray-MS/MS systems offer the additional advantages over the HPLC-MS/MS methods of no carryover between samples, low sample consumption and no chromatographic method development time.…”

Section: Micro/nanospray-ms/msmentioning

confidence: 99%

“…Extensive optimization of the sample clean up process would be expected to eliminate matrix ion suppression and direct interference from endogenous components or from metabolites of the dosed compound when attempting to perform a "columnless" MS/MS assay. Chen and coworkers [45] have successfully applied a nanoelectrospray-MS/MS method for the determination of a drug candidate, an M2 muscarinic receptor antagonist, in human plasma. Sample clean-up procedures consisted of protein precipitation followed by solid phase extraction (SPE) on a liquid handling robotic system.…”

Section: Micro/nanospray-ms/msmentioning

confidence: 99%

Fast Mass Spectrometry-Based Methodologies for Pharmaceutical Analyses

Hsieh¹,

Fukuda²,

Wingate³

et al. 2006

CCHTS

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Historically, most bioanalytical methods for drug analysis in pharmaceutical industry were developed using HPLC coupled with UV or fluorescence detection. However, there is a trend toward interfacing separation technologies with more sensitive tandem mass spectrometry (MS/MS)-based systems. MS/MS detection offers complete resolution of the parent compounds from their first pass metabolites to avoid extra efforts for separation and sample clean-up procedures resulting in shorter run times. With the increasing demand for ever faster screening, there is a continuing demand for bioanalytical methods possessing higher sample throughput for both in vitro and in vivo drug metabolism and pharmacokinetic evaluations to accelerate the discovery process. This review focuses on the current approaches for fast MS-based assays (cycle-time less than 5 min) of pharmaceuticals and their metabolites that have been reported in the peer-reviewed publications.

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“…[16][17][18] The preliminary experimental results revealed that the sample extracts from the PPT/SPE procedure for the basic drug were not suitable for flow injection mainly because of mismatch between the mobile phase and the extraction solvents as revealed from the above ion suppression experiment. Therefore, a guard LC column (2.1 Â 10 mm) was used to move the analyte and IS peaks from the solvent front (0.08 min).…”

Section: High-speed Lc/ms/msmentioning

confidence: 99%

A simplified protein precipitation/mixed‐mode cation‐exchange solid‐phase extraction, followed by high‐speed liquid chromatography/mass spectrometry, for the determination of a basic drug in human plasma

Xue

Akinsanya

Liu

et al. 2006

Rapid Comm Mass Spectrometry

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A simplified protein precipitation/mixed-mode cation-exchange solid-phase extraction (PPT/SPE) procedure has been investigated. A mixture of acetonitrile and methanol along with formic acid was used to precipitate plasma proteins prior to selectively extracting the basic drug. After vortexing and centrifugation, the supernatants were directly loaded onto an unconditioned Oasis MCX microElution 96-well extraction plate, where the protonated drug was retained on the negatively charged sorbent while interfering neutral lipids, steroids or other endogenous materials were washed away. Normal wash steps were deemed unnecessary and not used before sample elution. The sample extracts were analyzed under both conventional and high-speed liquid chromatography/tandem mass spectrometry (LC/MS/MS) conditions to examine the feasibility of the PPT/SPE procedure for human plasma sample clean-up. For the conventional LC/MS/MS method, chromatographic separation was achieved on a C18, 2.1 x 50 mm column with gradient elution (k' = 5.5). The mobile phase contained 0.1% formic acid in water and 0.1% formic acid in acetonitrile. For the high-speed LC/MS/MS method, chromatographic separation was achieved on a C18, 2.1 x 10 mm guard column with gradient elution (k' = 2.2, Rt = 0.26 min). The mobile phase contained 0.1% formic acid in water and 0.001% trifluoroacetic acid in acetonitrile. Detection for both conventional and high-speed LC/MS/MS methods was by positive ion electrospray tandem mass spectrometry on a ThermoElectron Finnigan TSQ Quantum Ultra, where enhanced resolution (RP 2000; 0.2 amu) was used for high-speed LC/MS/MS. The standard curve, ranging from 0.5 to 100 ng/mL, was fitted to a 1/x weighted quadratic regression model. This combined PPT/SPE procedure effectively eliminated time-consuming sorbent conditioning and wash steps, which are essential for a conventional mixed-mode SPE procedure, but retained the advantages of both PPT (removal of plasma proteins) and mixed-mode SPE (analyte selectivity). The validation results demonstrated that this PPT/SPE procedure was well suited for both conventional and high-speed LC/MS/MS analyses. In comparison with a conventional mixed-mode SPE procedure, the simplified PPT/SPE process provided comparable sample extract purity. This simple sample clean-up procedure can be applied to other basic compounds with minor modifications of PPT solvents.

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

Cited by 13 publications

References 15 publications

Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease

Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease

Fast Mass Spectrometry-Based Methodologies for Pharmaceutical Analyses

A simplified protein precipitation/mixed‐mode cation‐exchange solid‐phase extraction, followed by high‐speed liquid chromatography/mass spectrometry, for the determination of a basic drug in human plasma

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