Hyphenated HPLC-NMR and its applications in drug discovery

Peng, Sean

doi:10.1002/1099-0801(200010)14:6<430::aid-bmc32>3.0.co;2-p

Cited by 40 publications

(4 citation statements)

References 48 publications

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“…87,88) The technical difficulties in linking micro and capillary separation techniques with nanospray MS are being solved and advances in this front can be expected. The use of microfluidic systems offers prospects for miniaturized chip separations and even the possibility of miniaturized mass spectrometers in the rather more distant future.…”

Section: Future Trends and Perspectivesmentioning

confidence: 99%

Current Developments in LC-MS for Pharmaceutical Analysis

Lim

Lord

2002

Biological & Pharmaceutical Bulletin

151

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Liquid chromatography-mass spectrometry (LC-MS) is an analytical technique that couples high resolution chromatographic separation with sensitive and specific mass spectrometric detection. This includes high performance liquid chromatography (HPLC)-MS, capillary electrophoresis (CE)-MS and more recently capillary electrochromatography (CEC)-MS. The technique is still fast developing, particularly in the mass spectrometry area, with vastly improved sensitivity and resolution. It is probably the most powerful technique currently available for pharmaceutical analysis.This review is intended as a discussion on the current developments of LC-MS in pharmaceutical analysis rather than a review of literature alone. Various LC-MS techniques will be described briefly and the advantages and disadvantages of each will be discussed. DEVELOPMENTS IN LC-MS Brief History of LC-MSThe last twenty years has seen a dramatic increase in the capabilities of MS. At the beginning of this period the invention of fast atom bombardment (FAB), by Barber et al. in 1981, 1) enabled easier analysis of involatile and thermally unstable molecules, especially those of biological interest. It may be argued that this technique acted as a catalyst for the development of other ionization techniques, such as matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI), applicable to such molecules.The combination of liquid chromatographic techniques with MS has been an important development. Early interfaces were concerned with coping with the potential of 1 l/min vapour in the MS ionisation source vacuum that would be generated by eluent from typical analytical columns flowing at 1 ml/min. This was achieved by evaporating solvent on a heated moving belt, 2,3) or the use of very low flows, such as direct liquid introduction 4,5) and continuousflow FAB (CF-FAB).6) Thermospray 7) and particle beam 8) interfaces were improved methods during the 1980s.Atmospheric Pressure Ionization (ESI and APCI) Over the last decade, ESI and atmospheric pressure chemical ionization (APCI), have become the dominant techniques superseding thermospray etc. and are likely to remain so for the foreseeable future being inherently the most suitable for analytes in solution presented to the MS. ESI was originally proposed by Dole,9) who suggested using charged droplets as a source of ions for MS and Fenn 10) pioneered its development as an ionization source for MS, leading to the first commercially available instrument in 1989.In essence, the electrospray process involves producing a fine spray of ionized droplets from the outlet of a capillary carrying a liquid stream, which may be eluent from HPLC, CE, CEC or direct infusion of sample solution. This is achieved by applying a high voltage (typically 3-5 kV) to the outlet of the capillary at the spray tip, which creates a high electric potential and causes the production of a fine mist of droplets. This occurs at atmospheric pressure, hence the term atmospheric pressure ionization (API), is used. Thi...

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Section: Future Trends and Perspectivesmentioning

confidence: 99%

Current Developments in LC-MS for Pharmaceutical Analysis

Lim

Lord

2002

Biological & Pharmaceutical Bulletin

151

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“…In such cases, time-consuming off-line isolation and purification may be performed for analysis by NMR spectroscopy. Although hyphenated LC-NMR has received much attention in drug metabolism study, NMR detection is still relatively insensitive compared to UV and MS detection (Peng, 2000). Accordingly, the LC-MS/MS method that can distinguish between isomeric metabolites arising from biotransformations with the addition of 16 mass units resulting from oxidation of the parent drug is very useful for the rapid characterization of small amounts of metabolites.…”

Section: Original Researchmentioning

confidence: 99%

Differentiation between isomeric oxidative metabolites of a piperidine‐containing drug by liquid chromatography–tandem mass spectrometry with stable‐isotope tracer technique

Katô

Jingu

Ogawa

et al. 2001

Biomedical Chromatography

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This report describes the application of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to differentiation of hydroxylations and N-oxidations and of two different aliphatic hydroxylations in the investigation of the metabolism of pibutidine hydrochloride, a novel H2 antagonist, the structure of which includes a piperidine ring. Pibutidine metabolites in urine samples from adult male volunteers after oral administration of pibutidine hydrochloride were separated by reversed-phase LC and ionized using an electrospray ionization (ESI) interface. A hydroxylated form of pibutidine was distinguished from the N-oxide by comparison of their product ion spectra, although their mass-to-charge ratios of protonated molecules were identical. Further, two hydroxylated compounds were present in rat microsomal incubation mixtures with pibutidine. The distinction between their positions of hydroxylation (beta- and gamma-carbon hydroxylation) on the piperidine ring was studied using [piperidine-2H10] pibutidine as incubation substrate. The production of the beta-hydroxylated form was accompanied by the elimination of three 2H, resulting from a mechanism including the formation of iminium/enamine. The participation of the iminium ion intermediate in the beta-hydroxylation was confirmed by the observation that a cyanide adduct of pibutidine was formed instead of the beta-hydroxylated form when another incubation was performed in the presence of cyanide.

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“…Conventional methods of drug analysis such as chromatography [2], immunochromatography [3], mass spectrometry (MS) [4], nuclear magnetic resonance (NMR) [5], ultraviolet-visible spectroscopy (UV-Vis) [6], Fourier-transform infrared spectroscopy (FTIR) and IR [7], surface-enhanced Raman spectroscopy (SERS) and Raman [8], circular dichroism (CD) spectroscopy [9], and spectrofluorimetry [10], which can offer accurate and precise results, often lack portability, and can suffer from lengthy run times, high costs and complicated operation. Thus, new methods capable of providing rapid, specific responses whilst being cost effective and easy to use are still required [11,12].…”

Section: Introductionmentioning

confidence: 99%

Graphene-Based Electrochemical Sensors for Psychoactive Drugs

Boroujerdi

Paul

2022

Nanomaterials

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Sensors developed from nanomaterials are increasingly used in a variety of fields, from simple wearable or medical sensors to be used at home to monitor health, to more complicated sensors being used by border customs or aviation industries. In recent times, nanoparticle-based sensors have begun to revolutionize drug-detection techniques, mainly due to their affordability, ease of use and portability, compared to conventional chromatography techniques. Thin graphene layers provide a significantly high surface to weight ratio compared to other nanomaterials, a characteristic that has led to the design of more sensitive and reliable sensors. The exceptional properties of graphene coupled with its potential to be tuned to target specific molecules have made graphene-based sensors one of the most popular and well-researched sensing materials of the past two decades with applications in environmental monitoring, medical diagnostics, and industries. Here, we present a review of developments in the applications of graphene-based sensors in sensing drugs such as cocaine, morphine, methamphetamine, ketamine, tramadol and so forth in the past decade. We compare graphene sensors with other sensors developed from ultrathin two-dimensional materials, such as transition-metal dichalcogenides, hexagonal boron nitrate, and MXenes, to measure drugs directly and indirectly, in various samples.

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Hyphenated HPLC-NMR and its applications in drug discovery

Cited by 40 publications

References 48 publications

Current Developments in LC-MS for Pharmaceutical Analysis

Current Developments in LC-MS for Pharmaceutical Analysis

Differentiation between isomeric oxidative metabolites of a piperidine‐containing drug by liquid chromatography–tandem mass spectrometry with stable‐isotope tracer technique

Graphene-Based Electrochemical Sensors for Psychoactive Drugs

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