Application of RP-18 thin-layer chromatography and quantitative structure–activity relationship analysis for the prediction of the blood–brain barrier permeation

Sobańska, Anna W.; Brzezińska, Elżbieta

doi:10.1556/1006.2016.29.4.7

Cited by 10 publications

(39 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In total, a group of 154 structurally diverse molecules was investigated; this group included the set of 110 currently investigated structures. e log BB (B2) descriptors and chromatographic data (R f /PSA) exhibited a significant stability of the threshold limit between the CNS+ and CNS− compounds in all our experiments, involving a group of CNS+ drugs [21], CNS− inactive sunscreens, and excipients present in pharmaceutical and cosmetic preparations [22] and a large group of compounds of diverse structures and site of action [23].…”

Section: Introductionmentioning

confidence: 72%

“…e BBB permeability may be reflected by column and thin-layer chromatographic data (retention factors k, log k, R f , and R M , retention time t k , and retention volume V k ) [33][34][35][36][37][38][39][40][41]. Our earlier experiments [21][22][23] proved a close relationship between the RP-18 thin later chromatographic data and the CNS bioavailability. We proposed computational models of the BBB permeability based on multiple regression analysis (MR) and discriminant function analysis (DFA), involving thin-layer chromatographic descriptors R f and a novel parameter R f /PSA, supported by a set of physicochemical data.…”

Section: Introductionmentioning

confidence: 97%

“…e optimum threshold value is usually 0 to −1 [6,10,[17][18][19][20]. In our earlier studies, we considered the compounds with log BB ≥ −0.9 to be BBB+ [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…Having obtained such favorable results of the investigations involving the simple RP-18 TLC stationary phase, we wished to test the applicability of the RP-18 HPLC data obtained using the phase system as described earlier for the TLC models [21][22][23] in order to compare the applicability of the HPLC and TLC data to the BBB permeability modeling.…”

Section: Introductionmentioning

confidence: 99%

“…pH 7.4 phosphate-buffered saline was from Sigma-Aldrich. All of the analyzed compounds were investigated chromatographically and presented in previously defined populations [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

RP-18 HPLC Analysis of Drugs’ Ability to Cross the Blood-Brain Barrier

Sobańska

Hekner

Brzezińska

2019

Journal of Chemistry

Self Cite

View full text Add to dashboard Cite

One hundred ten compounds of diverse structures (actives and excipients used in pharmaceutical preparations) were studied by RP-18 HPLC with acetonitrile-pH 7.4 phosphate buffer 1 : 1 (v/v) as the mobile phase. The relationships between the BBB permeation coefficients and the chromatographic parameters log k and (log k)/PSA were compared to those between the blood-brain barrier (BBB) permeation parameters and the RP-18 TLC descriptors Rf and Rf/PSA known from our earlier studies. It was found that the correlations between the BBB permeability and the HPLC data are slightly worse than those achieved for the thin-layer chromatographic data. MLR analysis based upon the physicochemical data confirmed the value of the molecular descriptors, related to the CNS bioavailability. These variables, combined with the HPLC data, made it possible to generate computational models, explaining 70–96% of the total variance of the CNS bioavailability. Contrary to TLC Rf, the advantage of the modification of HPLC log k with PSA (polar surface area) has not been confirmed and the results obtained with log k are superior to those obtained after a novel (log k)/PSA parameter has been introduced. Establishing a firm threshold limit of (log k)/PSA, log k, or even k and k/PSA to distinguish between the CNS+ and CNS− compounds was impossible. On the other hand, discriminant function analyses involving log k and (log k)/PSA as discriminating variables separated the CNS+ and CNS− compounds with the success rate ca. 90%. On the basis of these results, it was concluded that the RP-18 HPLC analytical models are entirely successful in studies and predictions of the BBB permeability.

show abstract

Section: Introductionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 97%

“…e optimum threshold value is usually 0 to −1 [6,10,[17][18][19][20]. In our earlier studies, we considered the compounds with log BB ≥ −0.9 to be BBB+ [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…pH 7.4 phosphate-buffered saline was from Sigma-Aldrich. All of the analyzed compounds were investigated chromatographically and presented in previously defined populations [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations