Pharmacokinetic studies applications

Liu, A. et al.. Validated LC/MS/MS assay for curcumin and tetrahydrocurcumin in rat plasma and application to pharmacokinetic study of phospholipid complex of curcumin, J. Pharm. Biomed. Anal, 40, 720, 2006. 

Chapter 9 shows the importance of PLC in the critical field of medical research, with representative examples of the applications to amino acids, carbohydrates, lipids, and pharmacokinetic studies. 

These systems have been used in many bioanalytical applications. A Prospekt system coupled with MS quantitated eserine N-oxide, a cholinesterase inhibitor, in human plasma for low level (4.5 mg) oral administration pharmacokinetic studies (Pruvost et al. 2000). After conditioning of the SPE cartridge (PLRP-S, Spark) with methanol (5 mL/min, 0.5 min) and water (5 mL/min, 0.5 min), a volume of 250 jj.L plasma plus internal standard was injected and washed (water, 1 mL/min, 3 min). The analytes were flushed out with 80 20 ammonium acetate (20 mM, pH 3.5 adjusted with formic acid) and acetonitrile (0.3 mL/min) and separated on a Zobax SB-CN column (150 x 2.1 mm inner diameter, 5 jim). A calibration range of 25 pg/mL to 12.5 ng/mL was achieved with a run time of 10.5 min. 

Zarghi, A. et al. 2007. Quantification of carvedilol in human plasma by liquid chromatography using fluorescence detection Application in pharmacokinetic studies. J Pharm BiomedAnal. 44 250. 

Li, L., Sheng, Y., Zhang, J., Wang, C., and Guo, D.-A. (2004a). HPLC determination of four active saponins from Panax notoginseng in rat serum and its application to pharmacokinetic studies. Biomed. Chromatogr. 18,849-856. 

Srinivas NR, Shyu WC, Barbhaiya RH. 1995. Gas chromatographic determination of enantiomers as diastereo-mers following pre-column derivatization and applications to pharmacokinetic studies a review. Biomed Chromatogr 9 1. 

In an overview on CE for pharmaceutical applications, Altria describes the analysis of ionic salts, organic acids, and also water purity, which may have deleterious effects on synthetic processes. In her review, Natishan " also included indirect UV detection when performing pharmacokinetic studies. 

The types of trials to be undertaken demand a flexible approach, and depend on the seriousness of the disease, other therapeutic options and the pharmacokinetics at different ages. For example, if the disease process and efficacy endpoints are similar in adults and children, then an extrapolation from adult efficacy data, together with pharmacokinetic studies in the appropriate paediatric age range, together with safety studies, could form the basis of a successful application. Likewise, it may be possible to extrapolate efficacy from older to younger paediatric groups, with pharmacokinetic and safety studies in the relevant younger study subjects. Where there is no known correspondence between efficacy and... 

In vitro and in vivo pharmacokinetic studies with tretinoin cream and gel indicated that less than 0.3% of the topically applied dose is bioavailable. Circulating plasma levels of tretinoin are only slightly elevated above those found in healthy normal controls. Estimates of in vivo bioavailability ot Retin-A M/cro following single and multiple daily applications, for a period of 28 days with the 0.1 % gel, were... 

Hellenas, K. E., Nyman, A., Slanina, R, Loof, L., Gabrielsson, J. (1992). Determination of potato glycoalkaloids and their aglycone in blood serum by high-performance liquid chromatography. Application to pharmacokinetic studies in humans. J. Chromatogr, 573, 69-78. 

The idea of back transformation of a three-dimensional NMR experiment involving heteronuclear 3H/X/Y out-and-back coherence transfer can in principle be carried to the extreme by fixing the mixing time in both indirect domains. Even if one-dimensional experiments of this kind fall short of providing any information on heteronuclear chemical shifts, they may still serve to obtain isotope-filtered 3H NMR spectra. A potential application of this technique is the detection of appropriately labelled metabolites in metabolism studies, and a one dimensional variant of the double INEPT 111/X/Y sequence has in fact been applied to pharmacokinetics studies of doubly 13C, 15N labelled metabolites.46 Even if the pulse scheme relied exclusively on phase-cycling for coherence selection, a suppression of matrix signals by a factor of 104 proved feasible, and it is easily conceivable that the performance can still be improved by the application of pulsed field gradients. 

Results of pharmacokinetic studies of streptomycin are in most cases also applicable to dihydrostreptomycin and vice versa. In animals, the absorption of both streptomycin and dihydrostreptomycin is poor via the oral route but rapid after intramuscular administration. In cattle, peak serum levels were obtained 1 h after intramuscular injection of either streptomycin or dihydrostreptomycin (18), whereas serum concentrations produced in sheep and horses paralleled those obtained in cattle (19). As a result, most of an oral dose is recovered in the feces whereas most of a parenteral dose is recovered in the urine. However, if kidney function is severely impaired, little of an intramuscularly administered dose is excreted in the urine. 

Pharmacokinetic studies (e.g. plasma levels in dogs after peroral or intravenous application, tissue distribution in the rat after intravenous administration) with 44 in several animals have been carried out using l4C-labelled diphenylsilanediol and high pressure liquid chromatography. The elimination half-lives were found to be 1.7 h in mice, 7.2 h in rats, and 6.5 h in dogs after peroral application. 

Chen X, He H, Wang G, Yang B, Ren W, Ma L, Yu Q. 2007. Stereospecific determination of cis- and traws-resveratrol in rat plasma by HPLC Application to pharmacokinetic studies. Biomed Chromatogr 21 257-265. 

Z. Xie, Q. Liao, X. Xu, M. Yao, J. Wan, D. Liu, Rapid and sensitive determination of donepezil in human plasma by liquid chromatography/tandem mass spectrometry application to a pharmacokinetic study, Rapid Commun. Mass Spectrom. 20 (2006) 3193-3198. 

Y. Lu, H. Wen, W. Li, Y. Chi, Z. Zhang, Determination of donepezil hydrochloride (E2020) in plasma by liquid chromatography-mass spectrometry and its application to pharmacokinetic studies in healthy, young, Chinese subjects, J. Chromatogr. Sci. 42 (2004) 234-237. 

Although the scope of application continues to grow, the routine use of LC/MS technologies are now embraced by pharmaceutical researchers. Standard methods that incorporate highly specialized features are routinely developed for a variety of novel applications. Furthermore, many LC/MS applications that deal with quantitative bioanalysis (i.e., pharmacokinetics studies) are frequently outsourced to contract analytical laboratories. Thus, the routine use of LC/MS is a benchmarked commodity for drug development. 

Many examples exist for the integration of robotic mechanisms with analysis instruments. Automation is quite successful for sample preparation stages, such as SPE applications for pharmacokinetic studies and for the queuing of samples for instrument analysis. In many cases, significant savings are realized in human labor expense and the reduction of routine operations. Furthermore, consistent robotic operations afford increased precision via reproducibility of operations from sample to sample compared to manual operations. 

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