Effect of the counter-anion type and concentration on the liquid chromatography retention of β-blockers

Jones, A. D.; LoBrutto, Rosario; Kazakevich, Yuri

doi:10.1016/s0021-9673(02)00448-x

Cited by 88 publications

(47 citation statements)

References 18 publications

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“…Interestingly, Car is one of three agents currently approved for the treatment of heart failure (36), and may possess a survival advantage over other ␤AR antagonists (40). Although Alp is used in the treatment of hypertension, angina, and arrhythmia (41)(42)(43), its clinical efficacy in treating heart failure remains to be tested.…”

Section: Discussionmentioning

confidence: 99%

β-Blockers alprenolol and carvedilol stimulate β-arrestin-mediated EGFR transactivation

Kim¹,

Tilley²,

Chen³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

250

254

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Recent evidence suggests that binding of agonist to its cognate receptor initiates not only classical G protein-mediated signaling, but also ␤-arrestin-dependent signaling. One such ␤-arrestin-mediated pathway uses the ␤1-adrenergic receptor (␤1AR) to transactivate the EGFR. To determine whether ␤-adrenergic ligands that do not activate G protein signaling (i.e., ␤-blockers) can stabilize the ␤1AR in a signaling conformation, we screened 20 ␤-blockers for their ability to stimulate ␤-arrestin-mediated EGFR transactivation. Here we show that only alprenolol (Alp) and carvedilol (Car) induce ␤1AR-mediated transactivation of the EGFR and downstream ERK activation. By using mutants of the ␤1AR lacking G protein-coupled receptor kinase phosphorylation sites and siRNA directed against ␤-arrestin, we show that Alp-and Car-stimulated EGFR transactivation requires ␤1AR phosphorylation at consensus G protein-coupled receptor kinase sites and ␤-arrestin recruitment to the ligand-occupied receptor. Moreover, pharmacological inhibition of Src and EGFR blocked Alp-and Car-stimulated EGFR transactivation. Our findings demonstrate that Alp and Car are ligands that not only act as classical receptor antagonists, but can also stimulate signaling pathways in a G protein-independent, ␤-arrestin-dependent fashion.␤-adrenergic receptor ͉ G protein-coupled receptor ͉ signaling

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Section: Discussionmentioning

confidence: 99%

β-Blockers alprenolol and carvedilol stimulate β-arrestin-mediated EGFR transactivation

Kim¹,

Tilley²,

Chen³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

250

254

View full text Add to dashboard Cite

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“…The effect of TFA concentration-In principle, TFA can play three different roles in the cation-exchange separations studied here: (1) the proton from TFA, which at the concentrations employed here is almost fully dissociated, acts as the cationic displacer to exchange with cationic amines; (2) TFA in the mobile phase controls the pH and thus the charge status of the solutes; and (3) the trifluoroacetate resulting from the dissociation of TFA can act as an ion pairing agent in the mobile phase [5,6,38,39]. We believe that the third process has little effect on the retention of catecholamines because trifluoroacetate is not a sufficiently strong ion pairing agent to form ion pairs with the extremely hydrophilic catecholamines.…”

Section: 1the Separation Of Catecholaminesmentioning

confidence: 99%

Application of silica-based hyper-crosslinked sulfonate-modified reversed stationary phases for separating highly hydrophilic basic compounds

Luo

Paek

et al. 2008

Journal of Chromatography A

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The separation and determination of hydrophilic basic compounds are of great importance in many fields including clinical and biological research, pharmaceutical development and forensic analysis. However, the most widely used analytical separation technique in these disciplines, reversed-phase liquid chromatography (RPLC), usually does not provide sufficient retention for several of the important classes of highly hydrophilic basic compounds including catecholamines, many drug metabolites and many drugs of abuse. Commonly eluents having little or no organic modifier and/ or strong ion pairing agents must be used to achieve sufficient retention and separation. Use of highly aqueous eluents can lead to column failure by dewetting, resulting in poor retention, selectivity, reproducibility and slow recovery of performance. The use of a strong ion pairing agent to increase retention renders the separation incompatible with mass spectrometric detection and complicates preparative separations. This paper describes the successful applications of a novel type of silica-based, hyper-crosslinked, sulfonate-modified reversed stationary phase, denoted as − SO 3 -HC-C 8 -L, for the separation of highly hydrophilic cations and related compounds by a hydrophobically assisted cation-exchange mechanism. Compared to conventional reversed-phases, the − SO 3 -HC-C 8 -L phase showed significantly improved retention and separation selectivity. Concurrently, due to the presence of both cation-exchange and reversed-phase retention mechanisms and the high acid stability of hypercrosslinked phases, the separation can be optimized by changing the type or concentration of ionic additive or organic modifier, and by varying the column temperature. In addition, gradients generated by programming the concentration of either the ionic additive or the organic modifier can be applied to reduce the analysis time without compromising resolution. Furthermore, remarkably different chromatographic selectivities, especially toward cationic solutes, were observed upon comparison of the − SO 3 -HC-C 8 -L phase with conventional reversed-phases. We believe that the combination of these two types of stationary phases will be very useful in two-dimensional liquid chromatography.

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“…The retention factor in RPLC is related to the free energy of transferring the solute from the mobile phase to the stationary phase: (5) where B is the phase ratio, R is the universal gas constant, T is the temperature in Kelvin, m and s denote the mobile and stationary phases respectively. When pure water is used as the mobile phase (i.e.…”

Section: Discussion For the Effect Of Anionic Additives On Retention mentioning

confidence: 99%

“…Recently, less hydrophobic anionic additives (e.g. CF 3 COO -, ClO 4 -, PF 6 -) have gained in popularity for use with basic compounds and their influence on their retention mechanism has been the subject of extensive studies [4,5,7,9,16].…”

Section: Introductionmentioning

confidence: 99%

An unexpected observation concerning the effect of anionic additives on the retention behavior of basic drugs and peptides in reversed-phase liquid chromatography

Wang

Carr

2007

Journal of Chromatography A

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Anionic species with ion pair forming ability are commonly used to enhance the retention and efficiency of basic analytes in RPLC separations. However, little is known about the interactions between organic mobile phase modifiers and such ion pairing anions. In this work, we measured the magnitude of the retention increase of basic drugs and peptides upon addition of strong inorganic ion pairing anions (e.g. perchlorate) as a function of the volume fraction of modifier in acidic water-acetonitrile mobile phases on two different stationary phases. We found that the increase in retention upon addition of various salts depended strongly on the eluent strength. In general, larger retention increases upon addition of the anion were observed at higher organic fractions. Regression of retention against the volume fraction of organic modifier indicated that the ion pair forming anions substantially decreased S values while only slightly changing ln k' w values. The decrease in S is the major cause of the retention increase of basic drugs and peptides when such anions are added to the mobile phase.

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Effect of the counter-anion type and concentration on the liquid chromatography retention of β-blockers

Cited by 88 publications

References 18 publications

β-Blockers alprenolol and carvedilol stimulate β-arrestin-mediated EGFR transactivation

β-Blockers alprenolol and carvedilol stimulate β-arrestin-mediated EGFR transactivation

Application of silica-based hyper-crosslinked sulfonate-modified reversed stationary phases for separating highly hydrophilic basic compounds

An unexpected observation concerning the effect of anionic additives on the retention behavior of basic drugs and peptides in reversed-phase liquid chromatography

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