Rapid pKa estimation using vacuum‐assisted multiplexed capillary electrophoresis (VAMCE) with ultraviolet detection

Zhou, Caixia; Jin, Yingkun; Kenseth, Jeremy R.; Stella, Mark; Wehmeyer, Kenneth R.; Heineman, William R.

doi:10.1002/jps.20275

Cited by 70 publications

(36 citation statements)

References 49 publications

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“…Only a brief description of the instrument is given here; a more complete discussion can be found in earlier reports. 33,39,40 pH measurements were taken with a Ross 8102 combination glass electrode, equipped with an automatic temperature compensation (ATC) probe, using a Thermo Orion 520Aplus pH meter. The relative pH accuracy of the meter was specified to be AE0.002 pH units.…”

Section: Experimental Apparatusmentioning

confidence: 99%

“…There have been a number of methods employed for pK a measurements based on solubility, potentiometric titration, 7-10 spectrophotometry, [11][12][13][14] HPLC [15][16][17] and, most recently, on capillary electrophoresis (CE). [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] The solubility method is of limited accuracy and potentiometric titrations typically require mg amounts of pure sample with a throughput of 20-40 min per compound. 34 In addition, the sample concentrations required for potentiometry often result in precipitation of poorly soluble compounds, necessitating mixed solvent extrapolation methods and further impacting sample throughput.…”

Section: Introductionmentioning

confidence: 99%

“…39,40 Recently, the use of a 96-capillary array for the rapid measurement of pK a values for 96 different compounds (mostly monoprotic acids and bases) was demonstrated. 33 A measurement of 128-168 compounds in an 8 h period was achieved by simultaneously analyzing eight compounds over 12 pH values in a single CE run.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Shalaeva

Kenseth²,

Lombardo

et al. 2008

Journal of Pharmaceutical Sciences

184

117

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Section: Experimental Apparatusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Shalaeva

Kenseth²,

Lombardo

et al. 2008

Journal of Pharmaceutical Sciences

184

117

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“…For pH values below 6.0, significant fractions of flufenamate ion (pKa=4.27) 37 changes to the corresponding protonated form which is not detected by the electrode. For pH > 9.0, the hydroxide ion interferes with the electrode's response (Figure 2).…”

Section: Ph Effectmentioning

confidence: 95%

Development of a potentiometric flufenamate ISE and its application to pharmaceutical and clinical analyses

Santini¹,

Pezza²,

Oliveira³

et al. 2008

J. Braz. Chem. Soc.

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As características, o desempenho e a aplicação de um eletrodo do tipo Pt Hg Hg 2 (FF) 2 Grafite, FF=íon flufenamato, são descritas. O eletrodo responde a FF com sensibilidade de (-58,6 1,2) mV década -1 no intervalo de 1,0 10 -6 -1,0 10 -2 mol L -1 , a pH 6,0 -9,0 e com um limite de detecção de 7,1 10 -7 mol L -1 . O eletrodo é de custo relativamente baixo e facilmente construído, apresenta um rápido tempo de resposta (10-25 s) e pode ser usado por um período de 5 meses sem qualquer variação considerável nas suas características de desempenho. O eletrodo proposto mostrou boa seletividade para o íon flufenamato na presença de várias substâncias, bem como na presença de alguns carboxilatos e ânions inorgânicos. O eletrodo foi aplicado com sucesso na determinação de ácido flufenâmico em medicamentos e amostras de soro humano.The characteristics, performance, and application of an electrode, namely, Pt Hg Hg 2 (FF) 2 Graphite, where FF stands for flufenamate ion, are described. This electrode responds to FF with sensitivity of (-58.6 1.2) mV decade -1 over the range 1.0 10 -6 -1.0 10 -2 mol L -1 at pH 6.0 -9.0 and a detection limit of 7.1 10 -7 mol L -1. The electrode is easily constructed at a relatively low cost with fast response time (within 10-25 s) and can be used for a period of 5 months without any considerable change in its performance characteristics. The proposed electrode displayed good selectivity for flufenamate in the presence of several substances as well as in the presence of some carboxylate and inorganic anions. The electrode was successfully applied to the determination of flufenamic acid in pharmaceuticals and human serum samples.Keywords: flufenamate-sensitive electrode, potentiometry, dosage forms, blood serum IntroductionFlufenamic acid (FFA), [N-( , , -trifluoro-m-tolyl) anthranilic acid] is an analgesic, anti-inflammatory and antipyretic drug. It is extensively used in the treatment of arthritis and other illnesses related to muscular-skeletal problems.1 However the use of this drug has been implicated in some cases of nephrotoxicity.2 Due to the importance of the assay of FFA for pharmaceutical formulations and biological fluids, several analytical methods have been developed for the quantitative determination of this drug in both pharmaceutical and biological samples.These methods include spectrophotometry, 21,22 However, many of these methods are often time-consuming, technically demanding and require the use of costly, highly specialized instruments. Thus, there is an important demand for simple, low-cost, sensitive and rapid alternative methods for the determination of FFA in pharmaceuticals and biological fluids.Potentiometric methods with ion-selective electrodes (ISE's) have proved to be effective for the analysis of pharmaceutical formulations and biological samples, because these sensors offer the advantages of simple design, construction, and manipulation, reasonable selectivity, fast response time, applicability to colored and turbid solutions and possible interfacing with au...

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“…BGE constituents were tailored to individual compounds in order to minimize electromigration dispersion in indirect UV absorption detection mode. Finally, considerable effort has been made to improve the throughput of CZE for the determination of pK a by using pressure-assisted CE in single [6][7][8] or multiplexed [9] CE devices.…”

Section: Introductionmentioning

confidence: 99%

Determination of pK_a values of diastereomers of phosphinic pseudopeptides by CZE

et al. 2006

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A CE method was used for the determination of acidity constants (pK(a)) of a series of ten phosphinic pseudopeptides, which varied in number and type of ionogenic groups. Effective electrophoretic mobilities were measured in the 1.8-12.0 pH range in the BGEs of constant ionic strength of 25 mM. Effective electrophoretic mobilities, corrected to standard temperature of 25 degrees C, were subjected to non-linear regression analysis and the obtained apparent pK(a) values were recalculated to thermodynamic pK(a)'s by extrapolation to zero ionic strength according to the extended Debye-Hückel model. The pK(a) values of the phosphinic acid group fell typically in the 1.5-2.25 interval, C-terminal carboxylic groups in the 2.94-3.50 interval, carboxylic groups of the lateral chain of glutamate and aspartate in the 4.68-4.97 interval, imidazolyl moiety of histidine in the 6.55-8.32 interval, N-terminal amino groups in the 7.65-8.28 interval and epsilon-amino group of the lateral chain of lysine in the 10.46-10.61 interval. Further, separation of diastereomers of the phosphinic pseudopeptides was investigated in achiral BGEs. Evaluation of the resolution of the diastereomers as a function of pH of the BGE revealed that most suitable pH region for separation of the diastereomers is around the pK(a) values of the central phosphinic acid group of the pseudopeptides. Successful separation of some diastereomers was, however, achieved in the neutral and alkaline BGEs as well.

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Rapid pKa estimation using vacuum‐assisted multiplexed capillary electrophoresis (VAMCE) with ultraviolet detection

Cited by 70 publications

References 49 publications

Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Development of a potentiometric flufenamate ISE and its application to pharmaceutical and clinical analyses

Determination of pK_a values of diastereomers of phosphinic pseudopeptides by CZE

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Rapid pKa estimation using vacuum‐assisted multiplexed capillary electrophoresis (VAMCE) with ultraviolet detection

Cited by 70 publications

References 49 publications

Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Development of a potentiometric flufenamate ISE and its application to pharmaceutical and clinical analyses

Determination of pKa values of diastereomers of phosphinic pseudopeptides by CZE

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Product

Resources

About

Determination of pK_a values of diastereomers of phosphinic pseudopeptides by CZE