Development and validation of a liquid chromatographic–tandem mass spectrometric method for the determination of galantamine in human heparinised plasma

Verhaeghe, Tom; Diels, Luc; Vries, Ronald de; Meulder, Marc De; Jong, Jan de

doi:10.1016/s1570-0232(03)00129-6

Cited by 44 publications

(56 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…213 and 167, GAL and DPH) were selected in quadrupole 3 (Q3). The quantifier precursor to product ion (M+H) + transition of 288-to-213 m/z for GAL is shown in Figure 3 [31,32,34,35]. organic extraction solvent was used the P' for that solvent consisted of three main contributions, x e (interaction with ethanol -proton acceptors), x d (interaction with dioxane -proton donors) and x n (interaction with nitromethane -dipole-dipole interactions) that could be fine tuned for chromatographic separation integrity and extraction recovery selectivity.…”

Section: Mass Spectrometric Positive Ion Turbo Ionspray Mode Quantifimentioning

confidence: 99%

“…These assays all suffered from high plasma sample volume requirements, extended time consuming extraction procedures, low sensitivity, and low selectivity. Realizing these sample preparation and instrumental shortcomings researchers soon moved on to techniques that not only employed the separation power of LC but combined that with the low plasma sample requirement, high sensitivity, and high selectivity of triple quadrupole mass spectrometry (MS/MS) detection [30][31][32]. While these assays have shown a variety of improvements they have all been primarily developed for human plasma samples and have not been explored for the rapid extraction of therapeutic doses of GAL in guinea pig plasma.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An Extraction Assay Analysis for Galanthamine in Guinea Pig Plasma and its Application to Nerve Agent Countermeasures

Steiner¹

2012

J Anal Bioanal Techniques

View full text Add to dashboard Cite

Galanthamine hydrobromide (GAL HBr), approved material for treatment of mild to moderate Alzheimer's disease, is a centrally-acting reversible acetylcholinesterase inhibitor (AChEI) that is currently under evaluation as a therapeutic countermeasure against organophosphorus G-and V-Series nerve agents, which can induce rapid lethality in guinea pigs and humans. It has been shown that upon combination with atropine (ATR) and pyridine-2-aldoxime methochloride (2-PAM), a single dose of GAL administered before or soon after the acute exposure to a lethal dose of organophosphorus compounds can safely counteract toxicity in guinea pigs. To that end a new sample preparation extraction method analysis assay has been explored to enable future high-throughput, reproducible, and sensitive assays for the extraction of galanthamine in guinea pig plasma. Samples were prepared with diphenhydramine hydrochloride (DPH HCl) internal standard and recovered with 10 min liquid-liquid trichloromethane extractions. Samples were analyzed with a reversed phase liquid chromatographic column interfaced to a triple quadrupole mass spectrometer (LC/MS/MS) operating in the positive ion multiple reaction monitoring (MRM) Turbo Ionspray mode. Precursor to product ion (M+H) + transitions of 288-to-213 m/z and 256-to-167 m/z for GAL and DPH were observed, respectively. Sample run times of 1.50 min were achieved.

show abstract

Section: Mass Spectrometric Positive Ion Turbo Ionspray Mode Quantifimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An Extraction Assay Analysis for Galanthamine in Guinea Pig Plasma and its Application to Nerve Agent Countermeasures

Steiner¹

2012

J Anal Bioanal Techniques

View full text Add to dashboard Cite

show abstract

“…Huang et al used LC-UV to detect the down-field matrix peaks that caused ion suppression for the analyte of interest and modified the chromatographic condition [113]. Another approach for assessing consistent matrix effect among the individual matrix lots is to measure the consistency for the results obtained from sample from individual matrix lot (typically n > 6) [114][115][116][117][118][119][120][121][122][123]. One could argue that as long as the results (both back-calculated concentration and MS response) are consistent among the tested lots, matrix effects would not likely contribute negatively to the quantitation.…”

Section: Matrix Effects and Recoverymentioning

confidence: 99%

Critical Review of Development, Validation, and Transfer for High Throughput Bioanalytical LC-MS/MS Methods

Zhou¹,

Song²,

Tang³

et al. 2005

CPA

View full text Add to dashboard Cite

Swift growth in the use of LC-MS/MS for the analysis of drugs in biological matrices has been compelled by the need for timely and high-quality data at many stages in drug discovery and development process: from high throughput screening of drug candidates and rapid data generation for pre-clinical studies to almost 'real-time' analysis of clinical samples. Prompt and rational method development, validation, and transfer play a pivotal role in achieving the goals of "faster, better, and cheaper" for pharmacokinetic studies since this could easily account for more than 50% of the time and labor resources for a moderate-sized project. Strategy for rational method development, validation and transfer has been largely kept as institutional knowledge but rarely appeared in literature. In this review article, strategies for developing and validating robust high throughput LC-MS/MS methods will be critically reviewed and discussed. Automated sample preparation, fast chromatography, minimization of matrix effects, and strategy of narrowing the gap between validation and incurred sample analysis are just a few topics covered in this review. Other interesting approaches for improving method efficiency and ruggedness such as direct injection SPE and liquid/liquid extracts as well as multiplexing of LC columns will also be discussed. Potential pitfalls during method development and validation are pointed out. At the end, the question "how fast is fast enough and how fast is too fast?" will be answered after considering all aspects of the method development and validation.

show abstract

“…Various analytical methods were reported for the determination of galantamine, using techniques, such as micellar electrokinetic chromatography [3,4], capillary zone electrophoresis [5], HPLC-UV [6,7], HPLC-fluorescence detection or photodiode-array ra-diometric detection [8,9], high-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS) [10,11,12], and validated chiral LC method, for the enantiomeric separation of galantamine [13]. Galantamine hydrobromide is also listed in both United States Pharmacopoeia (USP) [14] and European Pharmacopoeia [15].…”

Section: Introductionmentioning

confidence: 99%

Semi-preparative isolation and characterization of a principal oxidative degradation product in galantamine hydrobromide by LC-ESI-MSⁿand 2D-NMR

Thomas¹,

Paul²,

Agarwal³

et al. 2014

Acta Chromatographica

View full text Add to dashboard Cite

Summary.Galantamine hydrobromide was subjected to oxidative stress degradation using hydrogen peroxide and analyzed as per the chromatographic conditions described in European Pharmacopoeia. The drug showed considerable degradation at ambient temperature resulting in the formation of two degradation products at relative retention times (RRTs) 0.63 and 2.52. The minor degradant at RRT 0.63 was identified as galantamine N-oxide. The principal degradant formed at RRT 2.52 was found to be unknown and has not been reported previously. The unknown impurity was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by isolation using semi-preparative high-performance liquid chromatography (HPLC). The isolated impurity was characterized using one-dimensional, two-dimensional nuclear magnetic resonance spectroscopy (1D and 2D NMR) and elemental analysis (EA). The principal degradant was found to be formed due to the generation of bromine and subsequent attack on the aromatic ring via in situ reaction between hydrogen bromide and hydrogen peroxide. The unknown impurity was characterized as (4aS,6R,8aS)-5,6,9,10,11,12-hexahydro-1-bromo-3-methoxy-11-methyl-4aH-[1]benzofuro [3a,3,2-ef] [2] benzazepin-6-ol.

show abstract

Development and validation of a liquid chromatographic–tandem mass spectrometric method for the determination of galantamine in human heparinised plasma

Cited by 44 publications

References 9 publications

An Extraction Assay Analysis for Galanthamine in Guinea Pig Plasma and its Application to Nerve Agent Countermeasures

An Extraction Assay Analysis for Galanthamine in Guinea Pig Plasma and its Application to Nerve Agent Countermeasures

Critical Review of Development, Validation, and Transfer for High Throughput Bioanalytical LC-MS/MS Methods

Semi-preparative isolation and characterization of a principal oxidative degradation product in galantamine hydrobromide by LC-ESI-MSⁿand 2D-NMR

Contact Info

Product

Resources

About

Development and validation of a liquid chromatographic–tandem mass spectrometric method for the determination of galantamine in human heparinised plasma

Cited by 44 publications

References 9 publications

An Extraction Assay Analysis for Galanthamine in Guinea Pig Plasma and its Application to Nerve Agent Countermeasures

An Extraction Assay Analysis for Galanthamine in Guinea Pig Plasma and its Application to Nerve Agent Countermeasures

Critical Review of Development, Validation, and Transfer for High Throughput Bioanalytical LC-MS/MS Methods

Semi-preparative isolation and characterization of a principal oxidative degradation product in galantamine hydrobromide by LC-ESI-MSnand 2D-NMR

Contact Info

Product

Resources

About

Semi-preparative isolation and characterization of a principal oxidative degradation product in galantamine hydrobromide by LC-ESI-MSⁿand 2D-NMR