New SRM Data Dependent Exclusion (MS)n Measurement for Structural Determination of Drug Metabolites Using LC/ESI/Ion Trap MS

Tozuka, Zenzaburo; Kaneko, Hayato; Shiraga, Toshifumi; Beppu, Manabu; Niwa, Toshiyuki; Kawamura, Akio; Kagayama, Akira

doi:10.2133/dmpk.18.390

Cited by 4 publications

(7 citation statements)

References 13 publications

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“…MS 3 product ion data require ion intensity of more than 10 4 in order to determine structure. 14) Thus, we decided to investigate in vitro metabolites in human liver microsomes using LIT-FTICRMS and subsequently analyze the metabolites in human plasma using LC/MS/MS after microdosing. A linear ion trap mass spectrometer may be used for qualification analysis and possible MS n measurement because it can trap specific ions.…”

Section: Discussionmentioning

confidence: 99%

Microdose Clinical Trial: Quantitative Determination of Nicardipine and Prediction of Metabolites in Human Plasma

Yamane¹,

Takami²,

Tozuka³

et al. 2009

Drug Metabolism and Pharmacokinetics

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A sample treatment procedure and high-sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for quantitative determination of nicardipine in human plasma were developed for a microdose clinical trial with nicardipine, a non-radioisotope labeled drug. The calibration curve was linear in the range of 1-500 pg/mL using 1 mL of plasma. Analytical method validation for the clinical dose, for which the calibration curve was linear in the range of 0.2-100 ng/mL using 20 microL of plasma, was also conducted. Each method was successfully applied to making determinations in plasma using LC/MS/MS after administration of a microdose (100 microg) and clinical dose (20 mg) to each of six healthy volunteers. We tested new approaches in the search for metabolites in plasma after microdosing. In vitro metabolites of nicardipine were characterized using linear ion trap-fourier transform ion cyclotron resonance mass spectrometry (LIT-FTICRMS) and the nine metabolites predicted to be in plasma were analyzed using LC/MS/MS. There is a strong possibility that analysis of metabolites by LC/MS/MS may advance to utilization in microdose clinical trials with non-radioisotope labeled drugs.

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Section: Discussionmentioning

confidence: 99%

Microdose Clinical Trial: Quantitative Determination of Nicardipine and Prediction of Metabolites in Human Plasma

Yamane¹,

Takami²,

Tozuka³

et al. 2009

Drug Metabolism and Pharmacokinetics

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“…The SRM data dependent MS n measurement 19) was programmed using the first scan at the selected m/z ions of the protonated molecules, the second CID scan at the selected m/z ions of the protonated molecules, and then 3 times data dependent CID measurement to cleave automatically only one fragment of the protonated molecule with the highest intensity.…”

Section: Measurement Of Lc Ms Electrospray Ionization (Esi) Msmentioning

confidence: 99%

“…The SRM data dependent exclusion MS n measurement 19) was programmed using the first scan at the selected m/z ions, the second MS/MS scan at the selected m/z ions of the protonated molecules, and then 3 times data dependent exclusion measurement to cleave automatically the all fragment of the protonated molecules. The SRM data dependent MS n measurement and the SRM data dependent exclusion MS n measurement were established for the structure determination of metabolites and an unchanged drug using MS n fragmentation in an ESI Ion Trap.…”

Section: Measurement Of Lc Ms Electrospray Ionization (Esi) Msmentioning

confidence: 99%

“…The SRM data dependent MS n measurement and the SRM data dependent exclusion MS n measurement were established for the structure determination of metabolites and an unchanged drug using MS n fragmentation in an ESI Ion Trap. 19), 25) 3. Results and Discussion 3.1 New SRM data dependent exclusion measurement of FK228 and its metabolites for structural determination using LC/ESI/Ion Trap MS We established the new SRM data dependent exclusion MS n measurement for structure determination of FK228 and its metabolites according to the following steps:…”

Section: Measurement Of Lc Ms Electrospray Ionization (Esi) Msmentioning

confidence: 99%

“…Recently, we described a strategy for e#ectively measuring drugs and small amounts of their metabolites using ESI Ion Trap MS, plus propose new methods for SRM data dependent MS n measurement and SRM data dependent exclusion MS n measurement. 19) We measured the mass spectra of FK228, its in vitro 14 metabolites, and in vivo 8 metabolites according to SRM data dependent exclusion MS n measurement and analyzed their fragmentation to determine their chemical structures. FK228 was estimated the two di#erent fragmentation pathways of which fragment ions had the di#erent composition of atoms.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

LTQ FT MS Accurate Mass and SRM Data Dependent Exclusion MSn Measurements for Structure Determination of FK228 and Its Metabolites

Tozuka

Strupat

Shiraga

et al. 2005

J. Mass Spectrom. Soc. Jpn.

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Comprehensive Quantitative and Qualitative Liquid Chromatography–Radioisotope–Mass Spectrometry Analysis for Safety Testing of Tolbutamide Metabolites Without Standard Samples

Tozuka

Aoyama

Nozawa

et al. 2011

Journal of Pharmaceutical Sciences

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New SRM Data Dependent Exclusion (MS)n Measurement for Structural Determination of Drug Metabolites Using LC/ESI/Ion Trap MS

Cited by 4 publications

References 13 publications

Microdose Clinical Trial: Quantitative Determination of Nicardipine and Prediction of Metabolites in Human Plasma

Microdose Clinical Trial: Quantitative Determination of Nicardipine and Prediction of Metabolites in Human Plasma

LTQ FT MS Accurate Mass and SRM Data Dependent Exclusion MSn Measurements for Structure Determination of FK228 and Its Metabolites

Comprehensive Quantitative and Qualitative Liquid Chromatography–Radioisotope–Mass Spectrometry Analysis for Safety Testing of Tolbutamide Metabolites Without Standard Samples

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