Estimation of angiotensin-converting enzyme inhibitors protein binding degree using chromatographic hydrophobicity data.

INTRODUCTION

Angiotensin-converting enzyme (ACE) inhibitors represent a significant group of drugs primarily used in the treatment of hypertension and congestive heart failure.

OBJECTIVE

Selected ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril) were studied in order to establish a fast and easy estimation method of their plasma protein binding degree based on their lipophilicity data.

METHODS

Chromatographic hydrophobicity data (parameter C0) were obtained on cellulose layers under conditions of normal-phase thin-layer chromatography (NPTLC), using different binary solvent systems. The ACE inhibitors lipophilicity descriptors (logP) values were calculated using the software package Virtual Computational Chemistry Laboratory.The ACE inhibitors plasma protein binding data were collected from relevant literature.

RESULTS

ACE inhibitors protein binding data varied from negligible (lisinopril) to 99% (fosinopril). The calculated lipophilicity descriptors, logP(KOWWIN) values ranged from -0.94 (lisinopril) to 6.61 (fosinopril). Good correlations were established between plasma protein binding values and calculated logP(KOWWIN) values (R2 = 0.8026) as well as chromatographic hydrophobicity data, C0 parameters (R2 = 0.7662). Even though good correlation coefficients (R2) were obtained in both relations, unacceptable probability value with p > 0.05 was found in relation between protein binding data and calculated logP(KOWWIN) values. Subsequently, taking into consideration the request for probability value lower than 0.05, a better relationship was observed between protein binding data and chromatographically obtained hydrophobicity parameters C0 values.

CONCLUSION

Cellulose layers are easily available and cost effective sorbent to assess hydrophobicity. Experimentally obtained data on ACE inhibitors hydrophobicity and plasma protein binding estimation are important parameters in evaluating bioavailability of these drugs.