Pharmaceutical application of liquid chromatography-mass spectrometry

Qin, Xue-Zhi; Tsai, Eric W.; Sakuma, Takeo; Ip, Dominic P.

doi:10.1016/0021-9673(94)00798-5

Cited by 48 publications

(28 citation statements)

References 19 publications

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“…Approaches to this problem have included electrochemical [3], conductive [4], refractive index [5–7] and fluorescence [8, 9] detection, but have been limited by poor sensitivity and selectivity. Methods based on chemical derivatization may complicate the analytical procedure [9–11], but when combined with indirect detection they offer the most promising strategy for the development of sensitive and specific analytical methods for this class of compounds [4, 12–15]. Importantly, the strong chelating properties of phosphates, including nucleotides, for particular metal ions can be exploited in detection assays.…”

Section: Introductionmentioning

confidence: 99%

Metal complexation chemistry used for phosphate and nucleotide determination: an investigation of the Yb3+–pyrocatechol violet sensor

et al. 2008

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Metal complexation reactions can be used effectively as sensors to measure concentrations of phosphate and phosphate analogs. Recently, a method was described for the detection of phosphate or ATP in aqueous solution based on the displacement by these ligands of pyrocatechol violet (PV) from a putative 2:1 (Yb3+)2PV complex. We have not been able to reproduce this stoichiometry and report this work in order to correct the coordination chemistry upon which sensor applications are based. In our work, colorimetric and spectrophotometric detection of phosphate was confirmed qualitatively (blue PV + Yb3+; yellow + Pi); however, the sequence of visual changes on the titration of PV with 2 equiv. of Yb3+ and back titration with ATP as described previously could not be reproduced. In contrast to the linear response to Pi that was reported previously, the absorbance response at 443 or 623 nm was found to be sigmoidal using the recommended 2:1 Yb3+:PV solution (100 µM:50 µM, pH 7, HEPES). Furthermore, both continuous variation titration and molar ratio analysis (Job plot) experiments are consistent with 1:1, not 2:1, YbPV complex stoichiometry at pH 7 in HEPES buffer, indicating that the deviation from linearity is produced by excess Yb3+. Indeed, using a 1:1 Yb3+:PV ratio produces a linear response in ΔAbs at 443 or 623 nm on back titration with analyte (phosphate or ATP). In addition, speciation analysis of the Yb–ATP system demonstrates that a 1:1 complex containing Yb3+ and ATP predominates in solution at µM metal ion and ATP concentrations. Paramagnetic1H NMR spectroscopy directly establishes the formation of Yb3+–solute complexes in dilute aqueous solution. The 1:1 YbPV complex can be used for the colorimetric measurement of phosphate and ATP concentrations from ~2 µM.

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Section: Introductionmentioning

confidence: 99%

Metal complexation chemistry used for phosphate and nucleotide determination: an investigation of the Yb3+–pyrocatechol violet sensor

et al. 2008

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“…Several high-performance liquid chromatographic methods based on post-or precolumn derivatization of bisphosphonates have been developed [3][4][5][6][7][8][9][10][11]. For example, Ion-pair chromatography with massspectrometric [12], refractive index [13] and conductometric [14] detection have been proposed. The anion-exchange chromatography with refractive index detection is recommended by British Pharmacopoeia for the determination of sodium alendronate [15].…”

Section: Introductionmentioning

confidence: 99%

Re-evaluated data of dissociation constants of alendronic, pamidronic and olpadronic acids

et al. 2009

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The dissociation constants of (4-amino-1-hydroxybutylidene)bisphosphonic (alendronic) acid, (3-(dimethylamino)-1-hydroxypropylidene)bisphosphonic (olpadronic) acid and (3-amino-1-hydroxypropylidene)bisphosphonic (pamidronic) acid were obtained in aqueous solutions (0.10 M KCl) and micellar solutions of cetylpyridinium chloride (0.10 M CPC) at 25.0°C. With the exception of the third dissociation constant of alendronic acid, the dissociation constants of alendronic, olpadronic and pamidronic acids in aqueous solutions matched literature data. The possibility of sodium alendronate determination by acid-base titration by NaOH solution was theoretically grounded on the basis of re-evaluated data of alendronic acid dissociation constants.

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“…São empregadas colunas de troca aniônica [62][63][64] . Qin e colaboradores 65 desenvolveram método para a determinação de alendronato (altamente polar e termolábil) em comprimidos utilizando cromatografia iônica acoplada a detector de massas, empregando interface do tipo íon-spray, operando no modo negativo. Observou-se neste estudo que a fragmentação dominante deste composto é a clivagem das ligações C-P.…”

Section: Cromatografia Líquida De Alta Eficiência (Hplc)unclassified

Bisfosfonatos: síntese, análises químicas e aplicações farmacológicas

Fernandes¹,

Leite²,

Lanças³

2005

Quím. Nova

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Recebido em 22/1/04; aceito em 13/8/04; publicado na web em 2/2/05 BISPHOSPHONATES: SYNTHESIS, CHEMICAL ANALYSIS AND PHARMACOLOGICAL APPLICATIONS. Bisphosphonates are drugs that have been widely used in different bone diseases, and have recently been used successfully against many parasites. Various synthetic routes to prepare different types of bisphosphonates have been described, with distinct potency and pharmacological activity. A number of analytical techniques are currently being used to analyze these drugs; among these, the high performance liquid chromatography (HPLC), with different systems of detection, is worth highlighting. However, the development of more sensitive methods is still necessary, once they are essential for bioavailability and bioequivalence studies. This paper reports the major synthesis routes, chemical analysis methodologies and pharmacological applications of bisphosphonates.Keywords: bisphosphonates; bone diseases; high performance liquid chromatography. INTRODUÇÃOOs bisfosfonatos (BP's) formam uma classe de substâncias quí-micas que apresenta uma ligação P-C-P em sua estrutura, e agem como inibidores da reabsorção óssea, mediada pelos osteoclastos. Estes compostos são extensivamente utilizados no tratamento de várias doenças ósseas, destacando-se a doença de Paget, a hipercalcemia maligna, a osteoporose e a doença metastática e osteolítica.São análogos químicos da substância endógena denominada ácido pirofosfórico (Figura 1), que no organismo se encontra como pirofosfato, um inibidor natural da reabsorção óssea. No entanto, essa substância não pode ser utilizada como agente terapêutico no tratamento de doenças ósseas, pois sofre uma rápida hidrólise enzimática. Os bisfosfonatos são seus análogos sintéticos, onde o átomo central de oxigênio é substituído por um de carbono. Essa modificação faz com que os BP's sejam mais resistentes à degradação enzimática, e possuam uma meia-vida biológica maior, suficiente para influenciar o metabolismo ósseo 1 .Diferentes substituintes ligados ao carbono central dão características únicas para cada fármaco (Figura 2). O grupo R1 fornece a afinidade dos BP's pelos cristais ósseos, enquanto o grupo R2 é responsável pela potência e atividade farmacológicas 2 . Segundo Shinoda 3 , a adição de um grupo hidroxila ao átomo de carbono na posição 1 aumenta a potência anti-reabsortiva. Derivados com um grupo amino no final da cadeia lateral são extremamente ativos. Além disso, o comprimento da cadeia lateral é também muito importante, sendo a maior atividade encontrada em compostos com quatro carbonos, como o alendronato. Mais recentemente tem sido demonstrado que o grupo amino não tem que estar localizado necessariamente no fim da cadeia. No entanto, ainda não está bem clara a relação existente entre estrutura e atividade, podendo-se dizer apenas que a estrutura P-C-P é fundamental para a atividade e que a intensidade do efeito é intensamente dependente da cadeia lateral. Os BP's são sintetizados por meio de uma grande variedade de rotas sintéticas. Estas...

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Pharmaceutical application of liquid chromatography-mass spectrometry

Cited by 48 publications

References 19 publications

Metal complexation chemistry used for phosphate and nucleotide determination: an investigation of the Yb3+–pyrocatechol violet sensor

Metal complexation chemistry used for phosphate and nucleotide determination: an investigation of the Yb3+–pyrocatechol violet sensor

Re-evaluated data of dissociation constants of alendronic, pamidronic and olpadronic acids

Bisfosfonatos: síntese, análises químicas e aplicações farmacológicas

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