RP-18 HPLC Analysis of Drugs’ Ability to Cross the Blood-Brain Barrier
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 paramet...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2019/5795402 |
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| author | Anna W. Sobańska Adam Hekner Elżbieta Brzezińska |
| author_facet | Anna W. Sobańska Adam Hekner Elżbieta Brzezińska |
| author_sort | Anna W. Sobańska |
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| description | 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. |
| format | Article |
| id | doaj-art-d593fd5a6afc4a5e8938d377d3146f0f |
| institution | OA Journals |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Journal of Chemistry |
| spelling | doaj-art-d593fd5a6afc4a5e8938d377d3146f0f2025-08-20T02:19:40ZengWileyJournal of Chemistry2090-90632090-90712019-01-01201910.1155/2019/57954025795402RP-18 HPLC Analysis of Drugs’ Ability to Cross the Blood-Brain BarrierAnna W. Sobańska0Adam Hekner1Elżbieta Brzezińska2Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Lodz, Ul. Muszyńskiego 1, 90-151 Łódź, PolandDepartment of Analytical Chemistry, Faculty of Pharmacy, Medical University of Lodz, Ul. Muszyńskiego 1, 90-151 Łódź, PolandDepartment of Analytical Chemistry, Faculty of Pharmacy, Medical University of Lodz, Ul. Muszyńskiego 1, 90-151 Łódź, PolandOne 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.http://dx.doi.org/10.1155/2019/5795402 |
| spellingShingle | Anna W. Sobańska Adam Hekner Elżbieta Brzezińska RP-18 HPLC Analysis of Drugs’ Ability to Cross the Blood-Brain Barrier Journal of Chemistry |
| title | RP-18 HPLC Analysis of Drugs’ Ability to Cross the Blood-Brain Barrier |
| title_full | RP-18 HPLC Analysis of Drugs’ Ability to Cross the Blood-Brain Barrier |
| title_fullStr | RP-18 HPLC Analysis of Drugs’ Ability to Cross the Blood-Brain Barrier |
| title_full_unstemmed | RP-18 HPLC Analysis of Drugs’ Ability to Cross the Blood-Brain Barrier |
| title_short | RP-18 HPLC Analysis of Drugs’ Ability to Cross the Blood-Brain Barrier |
| title_sort | rp 18 hplc analysis of drugs ability to cross the blood brain barrier |
| url | http://dx.doi.org/10.1155/2019/5795402 |
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