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RP-HPLC Determination of Lipophilicity of Beta-lactams Used in Treatment of CNS Infections

80 years have passed since Fleming published discovery of penicillin. Beta-lactams have been for years the safest and most efficient antibiotics owing it to the specific action on bacterial cell wall. Nowadays, beta-lactams are in their renaissance as multipotent agents against neurological diseases (e.g. amylotrophic lateral sclerosis, Alzheimer, Parkinson and prion diseases).1 Thus their lipophilicity, as major characteristic determining passage through blood-brain barrier, is of grate importance for their targeted delivery. Eight most commonly used beta-lactams for treatment of CNS infections (amoxicillin, ampicillin, benzylpenicillin, cloxacillin, cefuroxime, ceftazidime, ceftrixaone, cefotaxime) were analyzed on C18 XBridgeTM column (Waters, USA) using binary mobile phase of water and acetonitrile on Agilent 1100 HPLC. Using linear solvent strength model log kw0 and φ 0 were determined.2 Lipophilicity log P parameters were calculated using different programmes available on the Internet (ALOGPs, CLOGP, IA_logP, KowWin, MiLogP, MLOGP, XLOGP). Cloxacillin was the most lipophilic beta-lactam analyzed (log kw0 = 1.53). Generally penicillins had grater lipophilicity compared to cephalosporines. HPLC parameters log kw0 and φ 0 were correlated to calculated log P values and significant correlation of φ 0 and XlogP was observed. This RP-HPLC method is very quick and efficient for determining lipophilicity of different classes of beta-lactams. References: 1 Ji HF, Shen L, Zhang HY: Beta-lactam antibiotics are multipotent agents to combat neurological diseases. Biochem Biophys Res Commun, 2005 ; 333(3):661-3. 2 Kaliszan R: QSRR: quantitative structure-(chromatographic) retention relationships. Chem Rev, 2007 ; 107(7):3212-46.

HPLC; lipophilicity; beta-lactams

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