Tandem-in-Time Mass Spectrometry as a Quantitative Bioanalytical Tool

Rossi, David T.; Hoffman, Keith L.; Janiczek-Dolphin, Nancy; Bockbrader, Howard N.; Parker, T.D.

doi:10.1021/ac970247n

Cited by 16 publications

(10 citation statements)

References 16 publications

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“…To obtain optimum selectivity by almost completely suppressing the noise level, the MS/MS technique was applied to determine PGB‐ECF in hair. MS/MS demonstrates high selectivity and sensitivity and has been used to solve many quantitative bioanalytical problems, including trace quantitation of xenobiotics and other forensic and/or clinically significant analytes in different biological matrices …”

Section: Resultssupporting

confidence: 93%

“…MS/MS demonstrates high selectivity and sensitivity and has been used to solve many quantitative bioanalytical problems, including trace quantitation of xenobiotics and other forensic and/or clinically significant analytes in different biological matrices. [42][43][44][45][46] The PGB-ECF molecular ion (radical cation) is characterised by a 259 m/z value. It produces a very small peak in the mass spectrum and is not ideal for selection as the precursor ion.…”

Section: Discussionmentioning

confidence: 99%

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GC‐MS/MS detects potential pregabalin abuse in susceptible subjects’ hair

Ianni

Aroni

Gili

et al. 2018

Drug Testing and Analysis

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Pregabalin, a GABA analogue, binds to the alpha 2 delta subunit of voltage-dependent calcium channels. It is recognised as efficacious in pathologies such as epilepsy, neuropathic pain, and anxiety disorders. Since pregabalin prescriptions have increased worldwide, reports of its abuse have been accumulating, mainly in patients with opioid abuse disorders. The present study investigated potential pregabalin abuse by means of hair analysis, a matrix that provides valuable retrospective information. Half of the pool of 280 susceptible patients had been occasional drug users and were being monitored for driving licence renewals. The other 140 patients had a history of opiate dependency and were monitored to assess compliance with methadone therapy. In view of determining pregabalin in hair samples, it was extracted in methanol, successfully derivatised to give the ethyl chloroformate derivative, and finally pregabalin was analysed by gas chromatography-tandem mass spectrometry. Selectivity, linearity, limit of detection, limit of quantification, recovery, intra- and inter-day precision, and accuracy of the quantification procedure were appraised. Pregabalin limits of detection and quantification were 30 pg/mg and 50 pg/mg, respectively. We found 10.7% of hair samples from methadone patients and 4.29% from occasional drug users were positive to pregabalin without medical prescription. The mean pregabalin concentration in hair was higher than in consumers with medical indications (1.45 ng/mg vs 0.74 ng/mg). These results suggest that pregabalin possesses a significant abuse potential particularly among individuals attending opiate dependence services and that pregabalin abuse is a serious emerging issue, which should be carefully monitored.

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Section: Resultssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

GC‐MS/MS detects potential pregabalin abuse in susceptible subjects’ hair

Ianni

Aroni

Gili

et al. 2018

Drug Testing and Analysis

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“…Although literature reports that compare the suitability of different mass spectrometers for quantitative detection 25,26 are found for diazepines 27,28 or proteins, 29 no data is available for oligonucleotides. The dependence of signal intensity on analyte concentration was measured using (dT) 8 and (dT) 24 .…”

Section: Limit Of Detection and Quantitation In Esi-ms Of Oligonucleomentioning

confidence: 99%

Factors determining the performance of triple quadrupole, quadrupole ion trap and sector field mass spectrometers in electrospray ionization tandem mass spectrometry of oligonucleotides. 1. Comparison of performance characteristics

Premstaller

Ongania

Huber

2001

Rapid Comm Mass Spectrometry

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The performance of triple-stage quadrupole (TSQ), quadrupole ion trap (QIT), and double focusing sector field (DFSF) mass spectrometers for the generation of fragment ions to obtain sequence information about oligonucleotides was compared. Upon electrospray ionization (ESI), the charge-state distribution of candidate precursor ions not only varied significantly with the type of mass spectrometer, but also with the size and sequence of the investigated oligonucleotides. While concentration limits of detection for an octanucleotide were in the 100 pmol/L range on the QIT and in the 5-10 nmol/L range on the TSQ and DFSF instruments, those of a 24-mer were in the 2-13 nmol/L range on all three instruments. Reproducibility of mass determination, an important prerequisite for reliable identification of fragment ions, was highest on the TSQ with 0.0037% relative standard deviation over three days. Finally, the tandem mass spectra of a dimethoxytritylated pentanucleotide recorded on the three instruments were compared. Relatively simple spectra dominated by complete series of fragment ions of the (a-B) and w type were obtained on the QIT. Complete series of (a-B) and w ions were also observed on the TSQ. However, additional fragments belonging to the b, c, d, x and z series were found in the spectrum. In the spectrum recorded after in-source fragmentation in the DFSF, only fragments corresponding to the loss of a nucleobase and a complete series of w ions were observed. All three mass spectrometers were suitable for the generation of fragment ions, from which the complete nucleotide sequence of the pentanucleotide could be deduced.

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“…The high degree of specificity provided by selected reaction monitoring (SRM) is a recognized strength of triple-quadrupolebased instruments, but it is also a limitation. Several investigators have described the potential advantages of using full-scan-based acquisition for quantitative analysis using a variety of mass analyzers [3][4][5][6][7][8]. High among these advantages is the ability to acquire information without the need for specific methods to be developed beforehand.…”

mentioning

confidence: 99%

Quantitative-qualitative data acquisition using a benchtop orbitrap mass spectrometer

Bateman

Kellmann

Muenster

et al. 2009

J. Am. Soc. Mass Spectrom.

179

103

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Current approaches to discovery-stage drug metabolism studies (pharmacokinetics, microsomal stability, etc.) typically use triple-quadrupole-based approaches for quantitative analysis. This necessitates the optimization of parameters such as Q1 and Q3 m/z values, collision energy, and interface voltages. These studies detect only the specified compound and information about other components, such as metabolites, is lost. The ability to perform full-scan acquisition for quantitative analysis would eliminate the need for compound optimization while enabling the detection of metabolites and other non-drug-related endogenous components. Such an instrument would have to provide sensitivity, selectivity, dynamic range, and scan speed suitable for discovery-stage quantitative studies. In this study, a prototype benchtop Orbitrap-based mass analyzer was used to collect both quantitative and qualitative data from human microsomal incubation samples as well as rat plasma from pharmacokinetic studies. Instrumental parameters such as scan speed, resolution, and mass accuracy are discussed in relation to the requirements for a quantitative-qualitative workflow. The ability to perform highly selective quantitative analysis while simultaneously characterizing metabolites from both in vitro and in vivo studies is discussed.

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Tandem-in-Time Mass Spectrometry as a Quantitative Bioanalytical Tool

Cited by 16 publications

References 16 publications

GC‐MS/MS detects potential pregabalin abuse in susceptible subjects’ hair

GC‐MS/MS detects potential pregabalin abuse in susceptible subjects’ hair

Factors determining the performance of triple quadrupole, quadrupole ion trap and sector field mass spectrometers in electrospray ionization tandem mass spectrometry of oligonucleotides. 1. Comparison of performance characteristics

Quantitative-qualitative data acquisition using a benchtop orbitrap mass spectrometer

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