Updating of the OECD Test Guideline 107 “partition coefficient N-octanol/water”: OECD Laboratory Intercomparison Test on the HPLC method

Klein, W.; Kördel, Werner; Weiß, M.; Poremski, Heinz-Jochen

doi:10.1016/0045-6535(88)90227-5

Cited by 98 publications

(44 citation statements)

References 26 publications

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“…4. This indicates that the rapid and reliable determination of log P oct values not only for neutral and acidic compounds, but also for basic analytes with high pK a values (compounds 6-12, 46, 47, 49, 51, 52) is possible by RP-HPLC with XBridge TM Shield RP 18 column, which is highly stable over a wide pH range (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Until recently, reliable determination of log P oct by RP-HPLC was achieved only for neutral and acidic drugs on silica-based stationary phases with silanol deactivation, such as LC-ABZ 15) and Discovery RP Amide C16 phases (our previous studies).…”

Section: ϭ097)mentioning

confidence: 99%

“…Some workers have used isocratic log k values, measured in an appropriate mobile phase, as a lipophilicity parameter. [8][9][10] However, the majority of investigators use the capacity factors extrapolated to the 100% water (log k w ) condition in order to eliminate the effects of organic solvent. [11][12][13][14][15] Indeed, the log k W has been proved to be useful for the investigation of a series of solutes covering broad lipophilicity range.…”

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Lipophilicity Measurement of Drugs by Reversed Phase HPLC over Wide pH Range Using an Alkaline-Resistant Silica-Based Stationary Phase, XBridgeTM Shield RP18

et al. 2008

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The lipophilicity of solutes, conventionally expressed by their partition coefficient in the 1-octanol/water system (log P oct ), is of high significance from both physicochemical and pharmacological viewpoints.1,2) A number of intermolecular forces between a solute and its environment (i.e., solvents) determine the partitioning process and its equilibration. In pharmacology, the forces are particularly important because they control the migration of solutes (drugs) to biomembranes. Not a few studies have been reported on the relationship between log P oct and adsorption/permeation of drugs in cell cultures and/or tissue preparations. 3-7)The reference procedure to measure log P oct is shake-flask method. The method is, however, time-consuming and narrow in applicable range (ca. Ϫ3Ͻlog PϽ4). The reversedphase HPLC (RP-HPLC) came to be a promising alternative to the shake-flask method, because it has advantages such as high throughput rate (which is of key importance to pharmaceutical industry with a vast number of potential drug candidates), insensitivity to impurities and/or degradation products, broad applicable range, low sample consumption, good accuracy and automation possibilities. In RP-HPLC, lipophilicity indices are derived from the capacity factor log k, which is calculated from Eq. 1,where t r and t 0 are the retention times of the solute and of an unretained compound, respectively. Some workers have used isocratic log k values, measured in an appropriate mobile phase, as a lipophilicity parameter. 8-10) However, the majority of investigators use the capacity factors extrapolated to the 100% water (log k w ) condition in order to eliminate the effects of organic solvent.11-15) Indeed, the log k W has been proved to be useful for the investigation of a series of solutes covering broad lipophilicity range. Generally, the extrapolation is based on a quadratic relationship between the isocratic capacity factor log k and the volume fraction of organic solvent in the mobile phase, j.16) When methanol is used as an organic modifier, a linear relationship (Eq. 2) is often obtained for neutral solutes, 17,18) log kϭϪSjϩlog k wwhere S and log k w are the slope and the intercept of the regression curve, respectively. Until recently, most lipophilicity studies based on RP-HPLC had employed octadecyl silica (ODS) stationary phases 19,20) and silanol deactivated stationary phases. 15,21,22) As for ODS stationary phases, the correlations between log P oct and log k w (or log k) are generally good for structurally related solutes. 19,20) The decrease in correlation between them with increasing structural diversity of solutes is attributed to the specific interactions between the compounds and the residual silanol groups in such stationary phases. 23)Some studies have been done on silanol deactivated stationary phases, Supelcosil LC-ABZ and Discovery RP Amide C18, where their alkyl chains contain amide groups that electrostatically shield silanols from highly polar analytes. High correlations were found between log P ...

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Section: ϭ097)mentioning

confidence: 99%

mentioning

confidence: 99%

Lipophilicity Measurement of Drugs by Reversed Phase HPLC over Wide pH Range Using an Alkaline-Resistant Silica-Based Stationary Phase, XBridgeTM Shield RP18

et al. 2008

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“…39-45) e Estimated from logK ow (Andersson and Schräder 1999) according to Xia et al (2005) f Calculated from logK pdms/w (Xia et al 2005) g Estimated from logK ow (Klein et al 1988) according to Xia et al (2005) biphenyl from 4 to 5 weeks, were non-significant (Cochran 1950;Niemelä 1982). The toluene and benzothiophene estimates, however, significantly decreased when incubation was extended to 5 weeks.…”

Section: Resultsmentioning

confidence: 99%

Microplate MPN-enumeration of monocyclic- and dicyclic-aromatic hydrocarbon degraders via substrate phase-partitioning

Johnsen

Henriksen

2008

Biodegradation

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The high aqueous solubility of monoaromatic and some diaromatic oil components may hinder classical growth-based MPN enumeration of bacterial mono- and di-aromatics degraders because these aromatics are toxic in high concentrations. We developed a microplate MPN method for the enumeration of toluene-, xylene-, naphthalene-, biphenyl- and benzothiophene-degraders on the basis of phase-partitioning of substrate between a biologically inert organic phase and an aqueous mineral salt medium. This way, it was possible to maintain non-toxic, aqueous concentrations in the microplate wells. Depletion of aqueous aromatics by growth of the degraders was prevented by the continuous solubilization of aromatics from the silicone phase. The method was validated by MPN enumerating degrader cultures both with phase-partitioned aromatics and with tryptic soy broth as carbon sources. The applicability of the method was demonstrated by MPN-enumerating mono- and di-aromatic degraders in soils of varying hydrocarbon pre-exposure.

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“…Estas fases devem reproduzir as interações que ocorrem entre um composto e um sistema de solventes bifásico (n-octanol/água), usado na partição. Quanto mais lipofílico o composto, maiores as interações entre este e a fase estacionária e, consequentemente, maior o tempo de retenção do composto (Klein et al, 1988;Martel, 2008). Assim, deve-se construir uma curva de calibração para o sistema cromatográfico, a partir dos valores de logP conhecidos (no sistema n-octanol/água) em função dos correspondentes valores de log k' (fator de capacidade que expressa os correspondentes tempos de retenção).…”

Section: Métodos Cromatográficosunclassified

“…A obtenção de valores de coeficiente de partição por métodos cromatográficos, em especial usando HPLC, apresenta algumas vantagens, como: alta praticidade, velocidade e eficiência, pode ser aplicada a compostos sem elevado grau de pureza e pode ser aplicada a compostos que apresentam valores de logP entre 0 e 6 (Klein et al, 1988;Martel, 2008;Segan et al, 2016). Uma das limitações do HPLC é ter que garantir que o composto em estudo apresente o mesmo mecanismo de interação com a fase móvel/estacionária, que o grupo de compostos padrão usados para construir a curva de calibração do sistema cromatográfico (Pires, 1998;Dabrowska et al, 2011).…”

Section: Métodos Cromatográficosunclassified

Aplicação do conceito do par iônico e seus efeitos sobre a lipofilicidade de brometos de amônio quaternários estruturalmente análogos a procaína, com atividade de bloqueio da transmissão neuromuscular, para estudos de <i>(Q)SAR</i>

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Updating of the OECD Test Guideline 107 “partition coefficient N-octanol/water”: OECD Laboratory Intercomparison Test on the HPLC method

Cited by 98 publications

References 26 publications

Lipophilicity Measurement of Drugs by Reversed Phase HPLC over Wide pH Range Using an Alkaline-Resistant Silica-Based Stationary Phase, XBridgeTM Shield RP18

Lipophilicity Measurement of Drugs by Reversed Phase HPLC over Wide pH Range Using an Alkaline-Resistant Silica-Based Stationary Phase, XBridgeTM Shield RP18

Microplate MPN-enumeration of monocyclic- and dicyclic-aromatic hydrocarbon degraders via substrate phase-partitioning

Aplicação do conceito do par iônico e seus efeitos sobre a lipofilicidade de brometos de amônio quaternários estruturalmente análogos a procaína, com atividade de bloqueio da transmissão neuromuscular, para estudos de <i>(Q)SAR</i>

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