The effect of liquid chromatography eluents and additives on the positive ion responses of cocaine, benzoylecgonine, and ecgonine methyl ester using electrospray ionization

Jeanville, P.; Estapé, Estela S.; Jeanville, Ivette Torres-Negrón de

doi:10.1016/s1387-3806(03)00142-8

Cited by 18 publications

(15 citation statements)

References 30 publications

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“…This strongly supports the proposal that mechanisms other than in-solution ionization may be important in ion formation by the electrospray process [11,12]. Indeed, the pH of the liquid phase becomes a meaningless concept by the end of the electrospray process as a protonated molecule emerges from the final, highly charged, droplet into the gas phase [13].…”

Section: Resultssupporting

confidence: 78%

“…Similar kinetic control has not been reported for liquid phase ionization, and might not be expected because of the greater opportunity for equilibrium to be established in the liquid phase, particularly in the time scale of a HPLC analysis. It is well established that acids, such as formic acid, can be used as mobile phase modifiers in electrospray negative ionization, and several authors [11][12][13][14] have noted that compounds can be analyzed in electrospray positive ionization using high pH mobile phases with no loss of sensitivity compared with low pH mobile phases. This suggests that the degree of ionization (protonation) of analyte in solution may not be a critical factor in the electrospray ionization process.…”

mentioning

confidence: 99%

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Kinetic Control of Protonation in Electrospray Ionization

Joyce

Richards

2011

J. Am. Soc. Mass Spectrom.

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The site of protonation in a molecule can greatly affect the fragments observed in product ion MS/MS spectra. In electrospray positive ionization mass spectra, protonation usually occurs predominantly on the most basic site on the molecule to produce the thermodynamically favored protonated species. However, the literature is unclear whether liquid phase or gas phase thermodynamics has the greater influence. This paper describes the protonation and fragmentation behavior of crizotinib and two of its impurities. Crizotinib has two possible protonation sites, a pyridine nitrogen and a secondary amine, piperidine nitrogen; the former is the favored site in the gas phase and the latter the more favored site in the liquid phase. The impurities contain alkyl substitution on the piperidine nitrogen, producing tertiary amine species. Literature precedence suggests that in the liquid phase, the piperidine nitrogen is still the most basic site but, in the gas phase, the pyridine nitrogen and the piperidine nitrogen have very similar basicities. Fragmentation data for the three molecules suggest that the secondary and tertiary amines protonate preferentially and almost exclusively on different sites. We propose that the secondary amine protonates on the piperidine nitrogen (influenced by solution thermodynamics) and the two tertiary amine structures protonate on the pyridine nitrogen because of steric hindrance at the most basic site of the molecule, allowing kinetic control of the protonation process.

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Section: Resultssupporting

confidence: 78%

mentioning

confidence: 99%

Kinetic Control of Protonation in Electrospray Ionization

Joyce

Richards

2011

J. Am. Soc. Mass Spectrom.

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“…This arises by loss of 4-fluorobenzoic acid from the molecule which may occur in several ways and a similar loss of benzoic acid is observed with cocaine. [20] It was noted that the b (exo) isomer produced relatively more of the m/z 124 ion at a given fragmentor voltage. This may be due to the closer proximity of the equatorial ester carbonyl to the protonated nitrogen providing another pathway for elimination (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

The syntheses and characterization 3β‐(4‐fluorobenzoyloxy)tropane (fluorotropacocaine) and its 3α isomer

Kavanagh

Angelov

O’Brien

et al. 2011

Drug Testing and Analysis

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3β-(4-Fluorobenzoyloxy)tropane (3β-FBT, fluorotropacocaine) was first reported by Finnish authorities to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) via the Early Warning System (EWS) in 2008 and our own laboratory tentatively identified it in 2010 in several products purchased from head shops. Very little is known about this cocaine-like drug and, as no reference standards were available, we have synthesized and characterized both 3β-FBT and its 3α isomer for use as reference standards. The two compounds are separable by gas chromatography (GC) but their electron-impact (EI) mass spectra were found to be almost identical. ¹⁹F NMR spectroscopy was also found to be a useful technique for distinguishing the two isomers.

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“…However, our practical knowledge is growing due to the active contributions by bioanalytical chemists, as evidenced by the wide coverage of a number of published papers in this area [10,11,[86][87][88][89][90][91][92][93][94][95][96][97][98][99][100]. In one such published study of negative ESI of a carboxylic acid compound, both formic acid and ammonium formate in a water/acetonitrile mobile phase decreased analyte response, but the ammonium formate caused the more severe decrease [86].…”

Section: Mobile Phase Optimizationmentioning

confidence: 99%

LC-MS Development Strategies for Quantitative Bioanalysis

Jemal¹,

Xia²

2006

CDM

175

114

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Although quantitative bioanalysis using liquid chromatography in conjunction with atmospheric pressure ionization tandem mass spectrometry (LC-MS/MS) has been in use for approximately fifteen years, new concepts and technologies are continuously being introduced to enhance the multiple steps of quantitative LC-MS/MS bioanalysis. In this review article, we have focused on concepts and technologies that have recently been introduced to achieve further improvements in biological sample collection/storage and extraction, chromatography and mass spectrometric detection. Under these major headings, a number of specific topics are presented, summarizing the most recent findings in these areas. Included among the topics discussed are: off-line plasma extraction, on-line plasma extraction, enhanced mass resolution, atmospheric pressure photoionization, high-field asymmetric waveform ion mobility spectrometry, electron capture atmospheric pressure chemical ionization, enhancing MS detection via formation of anionic and cationic adducts, chemical derivatization, ultra-performance chromatography, hydrophilic interaction chromatography, and MS-friendly ion-pair reversed-phase chromatography. In the end, we discuss potential pitfalls in LC-MS/MS bioanalysis and the means to avoid them. Such pitfalls may occur due to mass spectral interference from metabolites or prodrugs, due to the use of inappropriate calibration standard and quality control samples for analysis involving unstable drugs or metabolites, and due to the wild card phenomenon commonly known as the matrix effect.

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The effect of liquid chromatography eluents and additives on the positive ion responses of cocaine, benzoylecgonine, and ecgonine methyl ester using electrospray ionization

Cited by 18 publications

References 30 publications

Kinetic Control of Protonation in Electrospray Ionization

Kinetic Control of Protonation in Electrospray Ionization

The syntheses and characterization 3β‐(4‐fluorobenzoyloxy)tropane (fluorotropacocaine) and its 3α isomer

LC-MS Development Strategies for Quantitative Bioanalysis

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