Separation of N-nitrosoamino acids by C18 reversed-phase ion-pair high-performance liquid chromatography and compatible detection by electrospray ionization mass spectrometry

Cheng, C.S. Agnes; Tsang, Chun Wai

doi:10.1016/s0021-9673(99)00610-x

Cited by 10 publications

(4 citation statements)

References 12 publications

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“…We sought to improve phosphopeptide retention under alkaline conditions through the use of aliphatic-functionalized quaternary amines as ion pairing agents, and found that tetrapropylammonium ion completely abrogated breakthrough of phosphopeptides; moreover, we observed that peptide elution order from the first dimension column was well correlated with both the degree of phosphorylation and relative acidic content (D and E) of phosphopeptides. Despite the successful use of ion pairing chromatography in the analysis of a wide range of molecule classes (50,54,97), we observed significant fraction-to-fraction overlap of phosphopeptides in RP-RP fractionation augmented with tetrapropylammonium formate, suggesting that further optimization will be required to utilize these compounds for the analysis of complex biological lysates.…”

Section: Discussionmentioning

confidence: 75%

Online Nanoflow Multidimensional Fractionation for High Efficiency Phosphopeptide Analysis

Ficarro

Zhang

Carrasco-Alfonso

et al. 2011

Molecular & Cellular Proteomics

110

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Despite intense, continued interest in global analyses of signaling cascades through mass spectrometry-based studies, the large-scale, systematic production of phosphoproteomics data has been hampered in-part by inefficient fractionation strategies subsequent to phosphopeptide enrichment. Here we explore two novel multidimensional fractionation strategies for analysis of phosphopeptides. In the first technique we utilize aliphatic ion pairing agents to improve retention of phosphopeptides at high pH in the first dimension of a twodimensional RP-RP. The second approach is based on the addition of strong anion exchange as the second dimension in a three-dimensional reversed phase ( Reversible phosphorylation plays a central role in the regulation of normal cell physiology. The strong links between aberrant signaling and human disease, along with the potential for specific inhibition of disrupted kinase activity, continue to drive efforts aimed at systematic and largescale analysis of phosphorylation in cells and tissues. Shortly after introduction of immobilized metal affinity chromatography (IMAC) 1 as an enrichment tool prior to mass spectrometry (MS) analysis (1-3), several laboratories demonstrated the feasibility of phosphopeptide identification and quantitation en masse (4 -7). In the ensuing years, despite widespread proliferation of improved and innovative (8 -14) phosphoproteomics methods, the field struggled with low specificity and poor reproducibility within and across protocols and laboratories. These limitations effectively made dynamic range a secondary issue for the majority of studies. Over the past ca. 5 years, the performance of phosphopeptide enrichment protocols and related methods has stabilized; in fact several groups (15-23) have successfully coupled phosphopeptide enrichment with online or offline fractionation schemes to achieve, in some cases, over 10,000 phosphopeptide identifications. Although these strategies provide for larger phosphosite catalogs, closer inspection reveals that the analytical efficiency, as measured by the number of phosphopeptide identifications per microgram of biological lysate consumed, has remained surprisingly consistent at Ϸ1-10 phosphopeptides/g across a wide range of sample types (Table I). One explanation is that the physicochemical properties of phosphopeptides render them less amenable to fractionation by commonly used techniques. For example, although the combination of strong cation exchange (SCX) with reversed phase (RP) has been tremendously successful for 1 The abbreviations used are: IMAC, immobilized metal affinity chromatography; AML, Acute Myeloid Leukemia; CAD, collisionally activated dissociation; ESI, electrospray ionization; FDR, False Discovery Rate; FL, FLT3 ligand; FLT3, FMS-like tyrosine kinase 3; LC/MS, liquid chromatography/mass spectrometry; Lm-OVA, Recombinant Listeria monocytogenes expressing chicken ovalbumin; ITD, internal tandem duplication; MS/MS, mass spectrometry/mass spectrometry or tandem mass spectrometry; NTA, nitrilotetra...

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Section: Discussionmentioning

confidence: 75%

Online Nanoflow Multidimensional Fractionation for High Efficiency Phosphopeptide Analysis

Ficarro

Zhang

Carrasco-Alfonso

et al. 2011

Molecular & Cellular Proteomics

110

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“…Taken together, the MS/MS experiments suggested the formation of nitrosotetrahydro-β-carbolines 9-12 which were most likely modified at the tetrahydropyrido nitrogen. It should be noted that syn-and anti-isomers of these nitroso compounds coeluted(26) and could not be differentiated by HPLC-MS.…”

mentioning

confidence: 98%

Degradation of Tetrahydro-β-carbolines in the Presence of Nitrite: HPLC−MS Analysis of the Reaction Products

Diem

Gutsche

Herderich

2001

J. Agric. Food Chem.

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Motivated by the identification of numerous novel tetrahydro-beta-carboline-carboxylic acids in food samples, we studied the reactions of tetrahydro-beta-carbolines in the presence of nitrosating agents. The anticipated formation of nitroso derivatives from unsubstituted tetrahydro-beta-carbolines, and from tetrahydro-beta-carboline-3-carboxylic acids was indicated by HPLC-MS/MS analysis and validated by the characteristic product ion spectra of the respective nitroso compounds. In addition, oxidative decarboxylation resulted in formation of the corresponding dihydro-beta-carbolines, and in the generation of the beta-carbolines harman or norharman. Subsequently, we studied the reactivity of tetrahydro-beta-carboline-1-carboxylic acids derived from the Pictet-Spengler condensation of indole amines with alpha-oxo acids. Again, in the presence of nitrosating agents the rapid disappearance of the starting material was obvious, but no nitroso derivatives could be observed. Instead, further HPLC-MS/MS studies demonstrated that dihydro-beta-carbolines were the major products of tetrahydro-beta-carboline-1-carboxylic acids. Finally, we demonstrated that freshly isolated nitroso-precursors spontaneously decomposed to yield harman alkaloids. In conclusion, we revealed that nitroso-tetrahydro-beta-carbolines can represent intermediates involved in the generation of beta-carbolines, and we established a novel pathway for the formation of harman alkaloids from nutritional tetrahydro-beta-carbolines.

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“…The use of many of these additives have generally been ruled out when liquid chromatography is coupled to a mass spectrometer because of the nonvolatility of the additives, resulting in suppression of ionization. However, some nonvolatile salts have been successfully used for IP-LC-MS. Cetyltrimethylammonium chloride has been used for the analysis of N-nitrosoamino acids [7] and low concentrations (50 -500 mM) of tetrabutylammonium bromide has been used for the analysis of cyclic nucleotides [8]. A solution to the compatibility issue has been to use more volatile amines, such as dimethylhexylamine, which has been used in the analysis of a metabolite of clodronate [9].…”

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confidence: 99%

Development of generic liquid chromatography-mass spectrometry methods using experimental design

Seto

Bateman

Gunter

2002

J. Am. Soc. Mass Spectrom.

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Separation of N-nitrosoamino acids by C18 reversed-phase ion-pair high-performance liquid chromatography and compatible detection by electrospray ionization mass spectrometry

Cited by 10 publications

References 12 publications

Online Nanoflow Multidimensional Fractionation for High Efficiency Phosphopeptide Analysis

Online Nanoflow Multidimensional Fractionation for High Efficiency Phosphopeptide Analysis

Degradation of Tetrahydro-β-carbolines in the Presence of Nitrite: HPLC−MS Analysis of the Reaction Products

Development of generic liquid chromatography-mass spectrometry methods using experimental design

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