Rp TLC Assay of the Lipophilicity of New Azathioprine Analogs

Abstract

& The lipophilicity parameters of azathioprine (P 20 ) and nineteen of its derivatives (P 1 -P 19 ) were determined experimentally (R M0 and log P TLC ) by reversed-phase thin-layer chromatography and were compared with theoretical values (log P calcd ) obtained using 9 computational methods. The parameter R M0 and specific hydrophobic surface area b were significantly intercorrelated showing a congeneric class of the azathioprine derivatives. The parameter R M0 was correlated with molecular descriptors (molar mass, molar volume, and molar refractivity) and was converted into the parameter log P TLC by use of a calibration curve obtained for five standards. The theoretical parameter log P calcd differed dramatically depending on the calculating programs. The log P calcd values were compared with experimental log P TLC values showing low prediction power of calculated programs for compounds P 1 -P 20 . All compounds P 1 -P 19 were more lipophilic than azathioprine. The determined parameters were discussed in the terms of the structure-lipophilicity relationships.

Pharmacokinetic Profiling and Simultaneous Determination of Thiopurine Immunosuppressants and Folic Acid by Chromatographic Methods

“…The corresponding linear correlation between chromatographic hydrophobicity parameters featured r = 0.93. Although limited data on hydrophobicity of immunosuppressants are available in literature, it should be pointed out that comparable data were obtained by various techniques [42,43,44].…”

Thin-Layer Chromatography on Reversed Phase in the Characterization of Retention Behaviour, Lipophilicity, and Pharmacokinetics of Cyanoacetamide Derivatives

“…Bearing in mind all of the above, it was assumed that the examined relationships can be improved by introducing additional molecular descriptors. 61,62 Using the online program Molinspiration, selected descriptors were determined, which fulfilled the modified rule of Lipinski: total polar surface molecules (TPSA), molecular mass (MW), molecular volume (V), number of hydrogen bond acceptors (nON), and the number of hydrogen bond donors (nONHN). In Table 7 values of Lipinski's molecular descriptors and TPSA and V are given.…”

Miniaturized shake-flask HPLC method for determination of distribution coefficient of drugs used in inflammatory bowel diseases

“…Prior to the development of novel FDC, a complete insight into physicochemical properties of active pharmaceutical ingredients (API), one of which is lipophilicity, is needed in order to evaluate the interactions of drugs with each other, as well as with the human organism (21). To best of our knowledge, the lipophilicity of these compounds was investigated using indirect chromatographic techniques such as thin-layer chromatography (22,23), as well as using the traditional shake-flask procedure with UV-Vis spectroscopy (24,25).…”