On-line liquid chromatography coupled with high field NMR and mass spectrometry (LC-NMR-MS): a new technique for drug metabolite structure elucidation

Burton, Keith I.; Everett, Jeremy R.; Newman, Michael; Pullen, Frank S.; Richards, Donald St. P.; Swanson, Alistair G.

doi:10.1016/s0731-7085(96)02034-1

Cited by 56 publications

(15 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prominent among these is the technique of HPLC-SPE-NMR, for which a SPE cartridge is used to trap multiple injections of a metabolite to enable sufficient accumulation for NMR measurement and thereby eliminating the eluent effect on 1 H NMR signals. Various studies successfully applied such a technique to identify the metabolites of drugs or bioactive compounds (Burton et al, 1997;Spraul et al, 2003;Godejohann et al, 2004;Sandvoss et al, 2005;Lai et al, 2010) and the constituents in complex natural products (Wang and Lee, 2005;Lam et al, 2007;Lee et al, 2007). In the present study, HPLC-SPE-TT-NMR, which equipped a liquid handler between SPE and NMR to transfer compound from SPE to a 2-mm NMR tube for NMR measurement, and HPLC-HRESIMS were applied to characterize the metabolites of (2S)-pterosin A (1) in rat urine, collected in 24 h after intragastrical oral administration (Brant and Remon, 1991).…”

Section: Introductionmentioning

confidence: 99%

Metabolism of (2S)-Pterosin A: Identification of the Phase I and Phase II Metabolites in Rat Urine

Lee¹,

Hsu²,

Kang³

et al. 2012

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:The metabolic profile of the potent hypoglycemic agent, (2S)-pterosin A (1), in rat urine via intragastrical oral administration was investigated. In total, 19 metabolites (M1-M19) were identified. Among these, 16 metabolites were characterized by high-performance liquid chromatography solid-phase extraction-tube transfer-NMR, and seven metabolites were further isolated from the treated urine to enable further structural determination. Twelve of these are new compounds. The phase I metabolites of 1 were formed via various oxidations at positions C-3, C-10, C-12, C-13, or C-1 followed by decarboxylation of C-10 or C-14, and lactonization at C-12/C-14 or C-14/C-12. The phase II metabolites were glucuronide conjugates from the parent compound or phase I metabolites. The major metabolites were found to be (2S)-14-O-glucuronylpterosin A (M9), (2S)-2-hydroxymethylpterosin E (M14), and (؎)-pterosin B (M19). Quantitative HPLC analysis of metabolites, based on similar UV absorption and use of the regression equation of 1, indicated that ϳ71% 1 was excreted as metabolites in rat urine.

show abstract

Section: Introductionmentioning

confidence: 99%

Metabolism of (2S)-Pterosin A: Identification of the Phase I and Phase II Metabolites in Rat Urine

Lee¹,

Hsu²,

Kang³

et al. 2012

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…Up to now, NMR and HPLC were recognized generally to be the most powerful tools for structure elucidation and analytic scale separation, respectively. Hence, the HPLC-NMR technique has been applied to study the metabolic profile of some drugs (Burton et al, 1997;Spraul et al, 2003). The HPLC-SPE-NMR technique has also been successfully applied in analysis of natural products (Wang and Lee, 2005;Lam et al, 2007;Lee et al, 2007) as well as in identification of certain metabolites (Godejohann et al, 2004;Sandvoss et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Metabolism of Dicentrine: Identification of the Phase I and Phase II Metabolites in Miniature Pig Urine

Lai¹,

Kuo²,

Chen³

et al. 2010

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:The metabolic profile of dicentrine, a selective ␣ 1 -adrenoceptor antagonist with potent antiarrhythmic and antihypertensive activities, in miniature pig urine via oral administration was investigated for the first time. The urine, collected after a single oral administration of dicentrine, was pretreated using solvent extraction and column chromatographic methods to identify the metabolites containing fractions. Twenty-four metabolites (MI-1-9 and MII-1-15), of which 21 compounds are new, were identified by mass spectrometry and high-performance liquid chromatography-diode array detector solid-phase extraction-NMR techniques. Of these, 14 metabolites (MI-5, MII-1 and 2, and MII-5-15) were further isolated for structure confirmation. The phase I metabolic transformations of dicentrine were found to be N-demethylation, N-oxidation, O-demethylation (9,10-OMe), O,O-demethylenation (1-OCH 2 O-2), and hydroxylation at the benzylic (C-4) and the aromatic (C-3) positions, whereas those for the phase II were O-glucuronidation and O-glucosylation of the phenolic group of the phase I metabolites.

show abstract

“…NMR Spectroscopy is typically run without hyphenation to a separation system but LC--NMR and LC--NMR--MS systems can be, and have been, used in metabonomics. [24] NMR spectrometers suitable for metabonomics and pharmacometabonomics experiments are generally available with a range of magnetic field strengths from 9.4 to 18.8 Tesla, equivalent to operating at radiofrequencies between 400 MHz and 800 MHz respectively, for 1 H NMR. Operating at increased field strength has several advantages including: 1) improved sensitivity of detection; 2) increased dispersion, or spreading out of the crowded metabolite signals.…”

Section: Conducting Pharmacometabonomics Experimentsmentioning

confidence: 99%

Pharmacometabonomics in Humans: A New Tool for Personalized Medicine

Everett¹

2015

Pharmacogenomics

View full text Add to dashboard Cite

/ SummaryPharmacogenomics is now over 50 years old and has had some impact in clinical practice, through its use to select patient subgroups who will enjoy efficacy without side effects when treated with certain drugs. However, pharmacogenomics, has had less impact than initially predicted. One reason for this is that many diseases, and the way in which the patients respond to drug treatments, have both genetic and environmental elements. Pure genomics is almost blind to the environmental elements. A new methodology has emerged, termed pharmacometabonomics that is concerned with the prediction of drug effects through the analysis of predose, biofluid metabolite profiles, which reflect both genetic and environmental influences on human physiology. In this review we will cover what pharmacometabonomics is, how it works, what applications exist and what the future might hold in this exciting new area

show abstract

On-line liquid chromatography coupled with high field NMR and mass spectrometry (LC-NMR-MS): a new technique for drug metabolite structure elucidation

Cited by 56 publications

References 5 publications

Metabolism of (2S)-Pterosin A: Identification of the Phase I and Phase II Metabolites in Rat Urine

Metabolism of (2S)-Pterosin A: Identification of the Phase I and Phase II Metabolites in Rat Urine

Metabolism of Dicentrine: Identification of the Phase I and Phase II Metabolites in Miniature Pig Urine

Pharmacometabonomics in Humans: A New Tool for Personalized Medicine

Contact Info

Product

Resources

About