Direct on-line hyphenation of capillary liquid chromatography to nuclear magnetic resonance spectroscopy: Practical aspects and application to drug metabolite identification

Sandvoß, Martin; Roberts, Andy D.; Ismail, Ismail M.; North, Stephanie E.

doi:10.1016/j.chroma.2003.11.105

Cited by 25 publications

(17 citation statements)

References 16 publications

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“…Exact mass of the metabolite was achieved by Fourier transform ion cyclotron resonance MS. In another study, analysis of diclofenac metabolites in hepatocyte incubations was achieved using capillary LC/NMR equipped with a micro-NMR probe [82]. The miniaturized system using micro-NMR probe increased the sensitivity of the instrument, enabling the detection of metabolites with limited quantity in medium to low complexity matrices without the need for SPE concentration.…”

Section: Challenges In Metabolite Identification In the Environmentmentioning

confidence: 99%

Pharmaceutical metabolites in the environment: Analytical challenges and ecological risks

Celiz

Tso

Aga

2009

Enviro Toxic and Chemistry

293

149

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Abstract-The occurrence of human and veterinary pharmaceuticals in the environment has been a subject of concern for the past decade because many of these emerging contaminants have been shown to persist in soil and water. Although recent studies indicate that pharmaceutical contaminants can pose long-term ecological risks, many of the investigations regarding risk assessment have only considered the ecotoxicity of the parent drug, with very little attention given to the potential contributions that metabolites may have. The scarcity of available environmental data on the human metabolites excreted into the environment or the microbial metabolites formed during environmental biodegradation of pharmaceutical residues can be attributed to the difficulty in analyzing trace amounts of previously unknown compounds in complex sample matrices. However, with the advent of highly sensitive and powerful analytical instrumentations that have become available commercially, it is likely that an increased number of pharmaceutical metabolites will be identified and included in environmental risk assessment. The present study will present a critical review of available literature on pharmaceutical metabolites, primarily focusing on their analysis and toxicological significance. It is also intended to provide an overview on the recent advances in analytical tools and strategies to facilitate metabolite identification in environmental samples. This review aims to provide insight on what future directions might be taken to help scientists in this challenging task of enhancing the available data on the fate, behavior, and ecotoxicity of pharmaceutical metabolites in the environment.

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Section: Challenges In Metabolite Identification In the Environmentmentioning

confidence: 99%

Pharmaceutical metabolites in the environment: Analytical challenges and ecological risks

Celiz

Tso

Aga

2009

Enviro Toxic and Chemistry

293

149

View full text Add to dashboard Cite

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“…Since temperature programming can be expected to affect the ionization process in electrospray ionization less than solvent gradients, tem-perature programmed LC-MS may in many cases be a better choice than using solvent gradient LC-MS, where addition of sheath liquids may be necessary to maintain the sensitivity throughout the gradient. Recently, low volume flow cells for NMR have become commercially available, and the combination of capillary LC and NMR seems very promising when the sample amount is limited [135]. By using temperature programming under isocratic conditions, the resonance shifts due to changes in solvent composition are avoided, and much lower detection limits may be achieved.…”

Section: Instrumentationmentioning

confidence: 98%

Controlling the retention in capillary LC with solvents, temperature, and electric fields

Jandera

Blomberg

Lundanes³

2004

J of Separation Science

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Once a suitable stationary phase and column dimensions have been selected, the retention in liquid chromatography (LC) is traditionally adjusted by controlling the mobile phase composition. Solvent gradients enable achievement of good separation selectivity while decreasing the separation time as compared to isocratic elution. Capillary columns allow use of other programming parameters, i.e. temperature and applied electric fields, in addition to solvent gradient elution. This paper presents a review of programmed separation techniques in miniaturized LC, including retention modeling and method transfer from the conventional to micro- and capillary scales. The impact of miniaturized instrumentation on retention and the limitations of capillary LC are discussed. Special attention is focused on the gradient dwell volume effects, which are more important in micro-LC techniques than in conventional analytical LC and may cause significant increase in the time of analysis, unless special instrumentation and (or) pre-column flow-splitting is used. The influence of temperature upon retention is also discussed, and applications where the temperature has been actively used for retention control in capillary LC are included together with the instrumentation utilized. Finally the possibilities of additional selectivity control by applying an electric field over a packed capillary LC column are discussed.

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“…Analytical (4.6 mm) columns can support larger injections but also dilute the eluted sample as presented to the NMR detection region. The combination of HPLC and online SPE (70,71) for concentration of dilute samples prior to introduction to a capillary or cryogenic (72) probe NMR appears the best current alternative to full (73) or partial (74) offline isolation. In a very rare case, X-ray crystallography (75) can be used to exactly define metabolite stereochemistry in systems where even NMR fails to define all atom positions.…”

Section: Nmr and Structure Confirmationmentioning

confidence: 99%

Analytical Tools and Approaches for Metabolite Identification in Early Drug Discovery

Chen¹,

Monshouwer²,

Fitch³

2006

Pharm Res

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Determination of the chemical structures of metabolites is a critical part of the early pharmaceutical discovery process. Understanding the structures of metabolites is useful both for optimizing the metabolic stability of a drug as well as rationalizing the drug safety profile. This review describes the current state of the art in this endeavor. The likely outcome of metabolism is first predicted by comparison to the literature. Then metabolites are synthesized in a variety of in vitro systems. The various approaches to LC/UV/MS are applied to learn information about these metabolites and structure hypotheses are made. Structures are confirmed by synthesis or NMR. The special topic of reactive metabolite structure determination is briefly addressed.

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Direct on-line hyphenation of capillary liquid chromatography to nuclear magnetic resonance spectroscopy: Practical aspects and application to drug metabolite identification

Cited by 25 publications

References 16 publications

Pharmaceutical metabolites in the environment: Analytical challenges and ecological risks

Pharmaceutical metabolites in the environment: Analytical challenges and ecological risks

Controlling the retention in capillary LC with solvents, temperature, and electric fields

Analytical Tools and Approaches for Metabolite Identification in Early Drug Discovery

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