Application of liquid chromatography–mass spectrometryn analyses to the characterization of novel glyburide metabolites formed in vitro

Tiller, Philip R.; Land, A. P.; Jardine, I.; Murphy, D.M; Sozio, R.; Ayrton, A.; Schaefer, William H.

doi:10.1016/s0021-9673(97)00881-9

Cited by 59 publications

(50 citation statements)

References 5 publications

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“…These fragment ions are consistent with the loss of either C 2 H 4 O or CO 2 + , affording a molecular weight assignment of 432 u (data not shown). This data suggests that the compound is one where both isophthalic moieties are replaced by adipic ones, making up for the exact difference of 40 u.…”

Section: Resultssupporting

confidence: 69%

“…The use of data-dependent analyses, where the mass spectrometer makes 'real-time' decisions about the experiment to be performed based on data just obtained, means that screening of unknown mixtures becomes routine. This approach has already proven of worth in the identification of unknown metabolites, 2 where the task is identical, namely to characterize a complex unknown mixture. With both molecular weight and structural data obtained, the ability to identify leached contaminants was enhanced, enabling a rapid assessment of which adhesives were most appropriate.…”

Section: Resultsmentioning

confidence: 99%

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Qualitative assessment of leachables using data‐dependent liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry

Tiller

Fallah

Wilson

et al. 1997

Rapid Commun. Mass Spectrom.

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Data-dependent liquid chromatography tandem mass spectrometry was utilized to identify leachables from adhesives used in pharmaceutical products. This approach affords a significant increase in the amount of data obtained from a single experiment. No information about the sample is needed a priori to perform these analyses. The data thus acquired speeded up the selection of the appropriate adhesive and shortened the development time of the drug product.

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Section: Resultssupporting

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Qualitative assessment of leachables using data‐dependent liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry

Tiller

Fallah

Wilson

et al. 1997

Rapid Commun. Mass Spectrom.

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“…The total run-time for compound separation and column equilibration was 15 min which is much shorter than in previously reported methods of 22 to 55 min. [23][24][25]. This shorter run time increased the throughput of the clinical study samples.…”

Section: Discussionmentioning

confidence: 99%

Validation of a sensitive LC–MS assay for quantification of glyburide and its metabolite 4-transhydroxy glyburide in plasma and urine: An OPRU Network study

Kirby

Hébert

Easterling

et al. 2007

Journal of Chromatography B

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Glyburide (glibenclamide, INN), a second generation sulfonylurea is widely used in the treatment of gestational diabetes mellitus (GDM). None of the previously reported analytical methods provide adequate sensitivity for the expected sub-nanogram/mL maternal and umbilical cord plasma concentrations of glyburide during pregnancy. We developed and validated a sensitive and low sample volume liquid chromatographic-mass spectrometric (LC-MS) method for simultaneous determination of glyburide (GLY) and its metabolite, 4-transhydroxy glyburide (M1) in human plasma (0.5 ml) or urine (0.1 ml). The limits of quantitation (LOQ) for GLY and M1 in plasma were 0.25 and 0.40 ng/mL, respectively whereas it was 1.06 ng/mL for M1 in urine. As measured by quality control samples, precision (% coefficient of variation) of the assay was < 15% whereas the accuracy (% deviation from expected) ranged from −10.1-14.3%. We found that the GLY metabolite, M1 is excreted in the urine as the glucuronide-conjugate.

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“…In so-called data-dependent experiments, with HPLC coupled to a tandem mass spectrometer, repetitive recording of MS spectra is interleaved with the selection and analysis of peaks for CID analysis (40). The amount of data generated by such experiments running on a continuous basis is overwhelming for manual interpretation, consequently automation is becoming essential.…”

Section: Automation Of Data Collection and Analysismentioning

confidence: 99%

Protein Identification by Mass Spectrometry

Baldwin

2004

Molecular & Cellular Proteomics

195

124

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During the past two decades, mass spectrometry has become established as the primary method for protein identification from complex mixtures of biological origin. This is largely attributable to the fortunate coincidence of instrumental advances that allow routine analysis of minute amounts (typically femtomoles) of involatile, polar compounds such as peptides in complex mixtures, with the rapid growth in genomic databases that are amenable to searching with mass spectrometry (MS) 1 data. Like many other developing fields in science, the creation of techniques and software tools and the initial generation and interpretation of data have been the domain of experts, people who are cognizant not only of the benefits of the methods but also of their actual and potential weaknesses. Now, as mass spectrometric techniques and proteomic tools become increasingly available and accessible, a much broader range of researchers is applying the same methodology, often with substantially less understanding of the major limitations that critically affect the reliability and significance of the results. Ideally, the MS community should establish criteria for mass spectrometric identification of proteins that should be employed by researchers. As this remains a rapidly developing field with many different experimental approaches and different ways of searching and interpreting the data, it is difficult to promulgate hard and fast rules. Nevertheless, Molecular & Cellular Proteomics is attempting to develop standards of acceptability for proteomics papers, based on emerging knowledge as well as on principles of biological MS established over the last 20 years by the MS community. Authors of proteomics papers employing MS must make themselves fully aware of the key issues that are driving development of these guidelines. Hence, the paper that follows attempts to highlight the strengths and weaknesses of the methods in current use. It is particularly important to realize that for any protein match returned from a database search, there is a non-zero probability that it will be wrong. Many times, the quality of the data is such that the probability of a false positive can be disregarded, but in some cases the identifications returned by the search engines are very likely incorrect. Therefore, it is unacceptable to simply list all the hits that come back from any search engine and then discuss their biological significance as though they were categorically correct. PEPTIDE ANALYSISAlmost without exception, protein identification is based on the analysis of peptides generated by proteolyic digestion. The most widely used enzyme is trypsin, which hydrolyzes the protein on the C-terminal side of lysine and arginine, unless the subsequent amino acid in the sequence is a proline. This is advantageous as every peptide other than the protein C terminus has at least two sites for efficient protonation, the N-terminal amino group and the C-terminal basic residue, so peptides are readily ionized and detected as positive ions. However, for a v...

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Application of liquid chromatography–mass spectrometryn analyses to the characterization of novel glyburide metabolites formed in vitro

Cited by 59 publications

References 5 publications

Qualitative assessment of leachables using data‐dependent liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry

Qualitative assessment of leachables using data‐dependent liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry

Validation of a sensitive LC–MS assay for quantification of glyburide and its metabolite 4-transhydroxy glyburide in plasma and urine: An OPRU Network study

Protein Identification by Mass Spectrometry

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