Assessment of brain‐to‐blood drug distribution using liquid chromatography

Abstract

Delivery of already existing and new drugs under development to the brain necessitates passage across the blood-brain barrier (BBB) with its tight intercellular junctions, molecular components and transporter systems. Consequently, it is critical to identify the extent of brain permeation and the partitioning across the BBB. The interpretation of brain-to-blood ratios is considered to be a significant and fundamental approach for estimating drug penetration through BBB, the brain-targeting ability and central nervous system (CNS) pharmacokinetics. Among the different bioanalytical techniques, liquid chromatography with various detectors has been widely used for determination of these ratios. This review defines the different approaches for sample preparation, extraction techniques and liquid chromatography procedures concerned with the determination of drugs in blood and brain tissues and the assessment of brain-to-blood levels. These approaches are expanded to cover the analysis of several drug classes such as CNS-acting drugs, chemotherapeutics, antidiabetics, herbal medicinal products, radiopharmaceuticals, antibiotics and antivirals. Accordingly, stability in biological matrices and matrix effects are investigated.The different administration/formulation effects and the possible deviations in these ratios are also disscussed.

The Blood–Brain Barrier and Pharmacokinetic/Pharmacodynamic Optimization of Antibiotics for the Treatment of Central Nervous System Infections in Adults

“…The spectrum of activity varies considerably by antibiotic within each of the beta-lactam classes, and typical coverage of meningitis-associated organisms is listed in Table 1 . Beta-lactams are hydrophilic molecules and are highly ionized at a physiologic pH of 7.4 systemically and at 7.3, a typical pH within the CSF [ 19 , 38 , 39 , 40 ]. Together, these two chemical properties limit their penetration into the CSF through the intact blood–brain barrier [ 19 , 39 , 40 , 41 , 42 ].…”