Estimation of skin permeation by liquid chromatography

Soriano-Meseguer, Sara; Fuguet, Elisabet; Port, Adriana; Rosés, Martı́

doi:10.5599/admet.512

Cited by 18 publications

(11 citation statements)

References 21 publications

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“…In conclusion, although the PRISMA HT TM universal buffer solution suggests a working pH range between 3 and 10, it is advisable not to exceed pH 8 to avoid damaging the skin-PAMPA membrane. In that cases where permeability must be determined at pH values higher than eight (for example to determine the log P e of the neutral forms of bases with pK a values higher than 7) alternative methods should be used, such the estimation equations proposed by Zhang et al [18] or estimation through chromatographic measurements [24].…”

Section: Study Of Membrane Stabilitymentioning

confidence: 99%

Optimization of experimental conditions for skin-PAMPA measurements

et al. 2020

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In recent years, the parallel artificial membrane permeability assay (PAMPA) has been extended for prediction of skin permeation by developing an artificial membrane which mimics the stratum corneum structure, skin-PAMPA. In the present work, the different parameters affecting skin-PAMPA permeability, such as incubation time and stirring, have been studied to establish ideal assay conditions to generate quality data for a screening of active pharmaceutical ingredients (API) in early stage drug discovery. Another important parameter is membrane retention, which shows dependence on lipophilicity when compounds are in their neutral form. Furthermore, the stability of the membrane has been investigated at different pH values, especially at basic pHs. Finally, a good correlation between human skin permeability and skin-PAMPA permeability, with a large dataset (n = 46), has been established. The optimized assay conditions were an incubation time of 4 hours with stirring in a pH below 8. With all these considerations the thickness of the aqueous boundary layer is decreased as much as possible and the membrane stability is guaranteed.

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Section: Study Of Membrane Stabilitymentioning

confidence: 99%

Optimization of experimental conditions for skin-PAMPA measurements

et al. 2020

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“…The addition of the cosurfactant produced important differences between the mobility values obtained with or without it, although the reason for these differences has not been systematically studied. Taking into account that the retention factor of a substance in a given system is often used to estimate other of its properties, such as logPo/w [8][9][10][11] or biopartitioning parameters [20][21][22][23][24], it is very important to ensure it is determined correctly.…”

Section: Introductionmentioning

confidence: 99%

Determination of the retention factor of ionizable compounds in microemulsion electrokinetic chromatography

Fernández-Pumarega

Amézqueta

Fuguet

et al. 2019

Analytica Chimica Acta

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Determination of the retention factor of ionized compounds in microemulsion electrokinetic chromatography requires two mobility measurements at the same pH: one in the presence of the microemulsion and another in plain buffer. However, it has been observed that in some cases subtracting one mobility from another determined in a different medium leads to negative retention factors, which makes no sense from a chemical point of view. This indicates that there is some error in the process which has a direct impact when retention factors are used for further applications. Here, we evaluate how the components of the microemulsion confer different properties to the buffer medium, particularly varying the viscosity parameter (which is inversely related to mobility). Whereas sodium dodecyl sulfate, the surfactant used in the microemulsion, has little effect on the medium viscosity (only an increase of 5%-6%), the presence of 1-butanol, used as a stabilizer, increases it by around 30%. Meanwhile, heptane, which is used as an oil, provokes a slight decrease. Consequently, the mobilities obtained in the microemulsion system are shifted to higher values (less negative mobilities) compared to mobilities obtained in the aqueous buffer, and so one cannot be directly subtracted from the other. Since the microemulsion-buffer medium cannot be directly reproduced, we propose a correction that takes into account the variation of viscosities. This is determined from the electrophoretic mobility of the benzoate ion. As this ion does not interact with the microemulsion, the ratio of its mobilities (measured in plain buffer and microemulsion) is equivalent to the ratio of viscosities, and can be used as the correction factor for other measurements. Thus, mobilities in buffer and microemulsion media are placed on the same scale, overcoming the errors in retention factor determination.

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“…Chromatographic systems based on different techniques such as high performance liquid chromatography (HPLC) and electrokinetic chromatography (EKC) have been widely used to determine biopartitioning properties [1][2][3][4][5][6]. In these systems, the compounds experience a partition between an aqueous phase and a stationary phase, for HPLC systems, or a pseudoestationary phase, for EKC systems, similar to the partition that compounds experience in a biological system.…”

Section: Introductionmentioning

confidence: 99%

Estimation of the octanol-water distribution coefficient of basic compounds by a cationic microemulsion electrokinetic chromatography system

et al. 2020

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The octanol-water partition coefficient (Po/w), or the octanol-water distribution coefficient (Do/w) for ionized compounds, is a key parameter in the drug development process. In a previous work, this parameter was estimated through the retention factor measurements in a sodium dodecyl sulfate (SDS) - microemulsion electrokinetic chromatography (MEEKC) system for acidic compounds. Nonetheless, when ionized basic compounds were analyzed, undesirable ion pairs were formed with the anionic surfactant and avoided a good estimation of log Do/w. For this reason, an alternative MEEKC system based on a cationic surfactant has been evaluated to estimate Po/w or Do/w of neutral compounds and ionized bases. To this end, it has been characterized through the solvation parameter model (SPM) and compared to the octanol-water partition system. Results pointed out that both systems show a similar partition behavior. Hence, the log Po/w of a set of neutral compounds has been successfully correlated against the logarithm of the retention factor (log k) determined in this MEEKC system. Then, the log Do/w of 6 model bases have been estimated at different pH values and they have been compared to data from the literature, determined by the reference shake-flask and potentiometric methods. Good agreement has been observed between the literature and the estimated values when the base is neutral or partially ionized (up to 99 % of ionization).

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Estimation of skin permeation by liquid chromatography

Cited by 18 publications

References 21 publications

Optimization of experimental conditions for skin-PAMPA measurements

Optimization of experimental conditions for skin-PAMPA measurements

Determination of the retention factor of ionizable compounds in microemulsion electrokinetic chromatography

Estimation of the octanol-water distribution coefficient of basic compounds by a cationic microemulsion electrokinetic chromatography system

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