Microdialysis pharmacokinetic analysis

Saisho Y, Umeda T (1991) Continuous monitoring of unbound flomoxef levels in rat blood using microdialysis and its new pharmacokinetic analysis. Chem Pharm Bull (Tokyo) 39 808-810. 

Many process mixtures, notably fermentations, require sample preconcentration, microdialysis, microfiltration, or ultrafiltration prior to analysis. A capillary mixer has been used as a sample preparation and enrichment technique in microchromatography of polycyclic aromatic hydrocarbons in water.8 Microdialysis to remove protein has been coupled to reversed phase chromatography to follow the pharmacokinetics of the metabolism of acetaminophen into acetaminophen-4-O-sulfate and acetaminophen-4-O-glucu-ronide.9 On-line ultrafiltration was used in a process monitor for Aspergillus niger fermentation.10... 

Morrison PF, Bungay PM, Hsiao JK, Ball BA, Mefford IN, et al. 1991. Quantitative microdialysis analysis of trasients and application to pharmacokinetics in brain. Microdialysis in the neurosciences. Robinson TE, Justice JB, editors. New York Elsevier pp. 47. 

Validation of a new intra-arterial microdialysis shunt probe for the estimation of pharmacokinetic parameters. Journal of Pharmaceutical and Biomedical Analysis, 31, 1109-1117. 

Microdialysis has also been used as a sampling method for measuring the concentration of drugs in human subcutaneous tissues for pharmacokinetic studies [50]. The microdialysates are simpler than other biological fluids and do not contain proteins, permitting their direct injection for analysis by liquid chromatography. 

Microdialysis coupled to mass spectrometry is a powerful technique for on-and off-line analysis, providing information on pharmacokinetics, drug transport, and metabolite formation. With the widespread availability of LC/ESI/MS instruments there has been a shift toward liquid chromatography and away from gas chromatography and flow injection. Electrospray is the ionization method of choice for most applications and tandem mass spectrometry has grown in popularity. Thermospray and cfFAB applications have been used with microdialysis, but are older, obsolete techniques. 

The combination of a pharmacodynamic model with a modem technique such as microdialysis is an attractive solution to assess pharmacokinetic/pharmacodyamic (PK/PD) relationships. Two separate stndies supported this idea. Esterom Solution is derived from the esterification of benzoylmethylecgonine (cocaine) and contains a mixture of components (McDonald and Lunte, 2003). This solution is intended to be a topical analgesic to relieve pain and increase the range of motion in patients with acute inflammation. A pharmacodynamic model can only provide information about the qualitative reduction in pain as a result of topical application of complete mixture. The dermal microdialysis analysis of tins mixture revealed that the only component that penetrated the skin was hydroxypropyl braizoylecgonine (McDonald and Lunte, 2003). Thus, the analgesic activity of the I Lstcrom Solution was caused by one component. 

Off-line analysis of microdialysis samples was first used to monitor the pharmacokinetics of L-dopa [65]. In this example, a flexible probe was employed for I.V. microdialysis sampling. The probe was perfused at 1 pl/min. Five microliter samples were collected for analysis, leading to a temporal resolution of 5 min. The concentration of L-dopa in the blood was monitored for over... 

Microdialysis with off-line analysis has also been successfully employed for the investigation of the pharmacokinetics of an enantiomeric drug, isoproterenol [68,69]. CE has been shown to be an extremely powerful method for the separation of enantiomeric compounds. It is possible to place the chiral selector in the run buffer, precluding the need for very expensive modified LC columns. Due to the small volume requiranenfs of CE, very little additive is required. 

Lunte, S.M. Malone, M.A. Zou, H. Capillary Electrophoresis/Electrochemistry for the Analysis of Microdialysis Samples. Current Separations 1994 13, 75-79. O Shea, T.J. Telting-Diaz, M.W. Lunte, S.M. Lunte, C.E. Smyth, M.R. Capillary Electrophoresis-Electrochemistry of Microdialysis Samples for Pharmacokinetic Smdies. Electroanalysis 1992 4, 463 68. 

There are two main reasons for entering the realm of micro- and nano-LC to obtain necessary sensitivity or if only the smallest quantities of samples are available. The main fields of application are currently proteomics, pharmacokinetics, metabolism studies, microdialysis, and, increasingly, environmental analysis. Flow rates in micro- (2-50 pL min ) and nano-LC (200-2000 nL min ) place high demands on the HPLC system and the user. Continuous optimization with regard to robustness, sensitivity, detection limit, and resolution tends to be a feature of any application. 

Deleu D, Sarre S, Michotte Y, Ebinger G. Simultaneous in vivo microdialysis in plasma and skeletal muscle a study of the pharmacokinetic properties of levodopa by non-compartmental analysis. J Pharm Sd 1994 83 25-8. 

Microdialysis is used to collect solutes present in the extracellular fluid via a microdialysis probe with a semipermeable membrane at its tip (see Fig. 14.8). The probe is perfused by a buffer (perfusate), and solutes from the environment surrounding the probe diffuse though the membrane into the perfused solution. Perfusate with the solutes (dialysate) is then collected for ex situ analysis. Microdialysis has been used in vivo to monitor the local concentrations of solutes in the extracellular fluids in a number of different tissues. The first microdialysis experiments were conducted on the brain and blood plasma (Bito et al., 1966). It has since been used to study metabolism in numerous tissues such as brain, muscles, tendons, subcutaneous adipose tissue, lungs, kidneys, and liver (Flock and Kloft, 2005 de la Pena et al., 2000 Jackson, 2005 Siddiqui and Shuaib, 2001). Microdialysis is widely used for pharmacokinetic research (Davies, 1999 de Lange et al., 2000 Verbeeck, 2000) and has also been used to monitor cell metabolites in cell culture medium (Wu et al., 2001). 

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