Automated Chiral Analysis of Amino Acids Based on Chiral Derivatization and Trapped Ion Mobility–Mass Spectrometry

Will, Jonas M.; Behrens, Arne; Macke, Marcel; Quarles, C. Derrick; Kärst, Uwe

doi:10.1021/acs.analchem.0c03481

Cited by 38 publications

(37 citation statements)

References 36 publications

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“…(S)-naproxen chloride ((S)-NAP) chiral derivatization of amino acids and TIMS-MS analysis was employed by Will's group [125]. Interestingly, the authors coupled an integrated chromatography system (ICS) to a TIMS-MS instrument.…”

Section: Separation Of Diastereomers After Cda Labelingmentioning

confidence: 99%

Indirect Enantioseparations: Recent Advances in Chiral Metabolomics for Biomedical Research

Bogos

Pralea

Moldovan

et al. 2022

IJMS

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Chiral metabolomics is starting to become a well-defined research field, powered by the recent advances in separation techniques. This review aimed to cover the most relevant advances in indirect enantioseparations of endogenous metabolites that were published over the last 10 years, including improvements and development of new chiral derivatizing agents, along with advances in separation methodologies. Moreover, special emphasis is put on exciting advances in separation techniques combined with mass spectrometry, such as chiral discrimination by ion-mobility mass spectrometry together with untargeted strategies for profiling of chiral metabolites in complex matrices. These advances signify a leap in chiral metabolomics technologies that will surely offer a solid base to better understand the specific roles of enantiomeric metabolites in systems biology.

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Section: Separation Of Diastereomers After Cda Labelingmentioning

confidence: 99%

Indirect Enantioseparations: Recent Advances in Chiral Metabolomics for Biomedical Research

Bogos

Pralea

Moldovan

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…28 A recent study by Karst et al successfully demonstrated the enantioseparation of eight proteinogenic AAs by chiral derivatization with (S)naproxen chloride (S-NAP) using TIMS−MS. 29 Despite continuous advances in chiral derivatization coupled with IM−MS, the resolution and sensitivity for simultaneous determination of all chiral proteinogenic AA enantiomers in a single analytical run can still be improved. To unlock the critical bottleneck, designing a universal chiral selector is especially important.…”

Section: ■ Introductionmentioning

confidence: 99%

Powerful Steroid-Based Chiral Selector for High-Throughput Enantiomeric Separation of α-Amino Acids Utilizing Ion Mobility–Mass Spectrometry

Zhou

Wang

et al. 2021

Anal. Chem.

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Stereospecific recognition of amino acids (AAs) plays a crucial role in chiral biomarker-based diagnosis and prognosis. Separation of AA enantiomers is a long and tedious task due to the requirement of AA derivatization prior to the chromatographic or electrophoretic steps which are also timeconsuming. Here, a mass-tagged chiral selector namedhigh reactivity and good enantiomeric resolution in regard to AAs was developed. After a quick and easy chemical derivatization step of AAs using 17β-EBC as the single chiral selector before ion mobility−mass spectrometry analysis, good enantiomer separation was achieved for 19 chiral proteinogenic AAs in a single analytical run (∼2 s). A linear calibration curve of enantiomeric excess was also established using [d 0 ]/[d 5 ]-17β-EBC. It was demonstrated to be capable of determining enantiomeric ratios down to 0.5% in the nanomolar range. 17β-EBC was successfully applied to investigate the absolute configuration of AAs among peptide drugs and detect trace levels of D-AAs in complex biological samples. These results indicated that [d 0 ]/[d 5 ]-17β-EBC may contribute to entail a valuable step forward in peptide drug quality control and discovering chiral disease biomarkers.

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“…To date, a number of analytical methods including liquid chromatography (LC), ,− gas chromatography (GC),and capillary electrophoresis (CE) − coupled with ultraviolet (UV), fluorescence (FL), and mass spectrometric (MS) detections have been developed for the targeted chiral analysis of HAs/AAs. Besides chromatographic techniques, ion mobility-mass spectrometry (IM-MS) has also been emerged as a promising method for gas phase chiral analysis of AAs. − To achieve separation, these methods employ either chiral derivatizing reagents (CDRs) or chiral stationary phases (CSPs). Recently, Takayama and co-workers proposed an efficient LC coupled with electrospray-ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF/MS) strategy for chiral metabolomics using selectively synthesized CDRs for different functional groups such as (S)-1-(4,6-dimethoxy-1,3,5-triazin-2-yl)pyrrolidin-3-amine (DMT-3(S)-Apy) for carboxylic acids and (S)-2,5-dioxopyrrolidin-1-yl-1-(4,6-dimethoxy-1,3,5-triazin-2-yl) pyrrolidine-2-carboxylate (DMT-(S)-Pro-OSu) for amines. , Although this methodology provides an extremely useful tool for chiral metabolomics, the requirement of different CDRs and derivatization protocols for each class of chiral metabolites limits its suitability for analyzing patient samples due to the limited amount of sample as well as the trace levels of enantiomeric forms that are typically present.…”

mentioning

confidence: 99%

Novel Strategy for Untargeted Chiral Metabolomics using Liquid Chromatography-High Resolution Tandem Mass Spectrometry

Pandey

Collins

et al. 2021

Anal. Chem.

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Stereospecific recognition of metabolites plays a significant role in the detection of potential disease biomarkers thereby providing new insights in diagnosis and prognosis. D-Hdroxy/amino acids are recognized as potential biomarkers in several metabolic disorders. Despite continuous advances in metabolomics technologies, the simultaneous measurement of different classes of enantiomeric metabolites in a single analytical run remains challenging. Here, we develop a novel strategy for untargeted chiral metabolomics of hydroxy/amine groups (−OH/–NH2) containing metabolites, including all hydroxy acids (HAs) and amino acids (AAs), by chiral derivatization coupled with liquid chromatography-high resolution tandem mass spectrometry (LC-HR-MS/MS). Diacetyl-tartaric anhydride (DATAN) was used for the simultaneous derivatization of–OH/–NH2 containing metabolites as well as the resulting diastereomers, and all the derivatized metabolites were resolved in a single analytical run. Data independent MS/MS acquisition (DIA) was applied to positively identify DATAN-labeled metabolites based on reagent specific diagnostic fragment ions. We discriminated chiral from achiral metabolites based on the reversal of elution order of D and L isomers derivatized with the enantiomeric pair (±) of DATAN in an untargeted manner. Using the developed strategy, a library of 301 standards that consisted of 214 chiral and 87 achiral metabolites were separated and detected in a single analytical run. This approach was then applied to investigate the enantioselective metabolic profile of the bone marrow (BM) and peripheral blood (PB) plasma samples from patients with acute myeloid leukemia (AML) at diagnosis and following completion of the induction phase of chemotherapeutic treatment. The sensitivity and selectivity of the developed method enabled the detection of trace levels of the D-enantiomer of HAs and AAs in primary plasma patient samples. Several of these metabolites were significantly altered in response to chemotherapy. The developed LC-HR-MS method entails a valuable step forward in chiral metabolomics.

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Automated Chiral Analysis of Amino Acids Based on Chiral Derivatization and Trapped Ion Mobility–Mass Spectrometry

Cited by 38 publications

References 36 publications

Indirect Enantioseparations: Recent Advances in Chiral Metabolomics for Biomedical Research

Indirect Enantioseparations: Recent Advances in Chiral Metabolomics for Biomedical Research

Powerful Steroid-Based Chiral Selector for High-Throughput Enantiomeric Separation of α-Amino Acids Utilizing Ion Mobility–Mass Spectrometry

Novel Strategy for Untargeted Chiral Metabolomics using Liquid Chromatography-High Resolution Tandem Mass Spectrometry

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