Pharmacokinetic studies quantification range

A selective, sensitive, and rapid hydrophilic interaction liquid chromatography with electrospray ionization tandem mass spectrometry was developed for the determination of donepezil in human plasma [32], Donepezil was twice extracted from human plasma using methyl-ferf-butyl ether at basic pH. The analytes were separated on an Atlantis HILIC Silica column with the mobile phase of acetonitrile ammonium formate (50 mM, pH 4.0) (85 15, v/v) and detected by tandem mass spectrometry in the selective reaction monitoring mode. The calibration curve was linear (r = 0.9994) over the concentration range of 0.10-50.0 ng/ ml and the lower limit of quantification was 0.1 ng/ml using 200 /d plasma sample. The CV and relative error for intra- and inter-assay at four quality control levels were 2.7% to 10.5% and —10.0% to 0.0%, respectively. There was no matrix effect for donepezil and cisapride. The present method was successfully applied to the pharmacokinetic study of donepezil after oral dose of donepezil hydrochloride (10 mg tablet) to male healthy volunteers. 

Pharmacotoxic and pharmacokinetic studies carried out for the new antitumor drug Aviscumine (rViscumin) were supported by a robust quantitative IPCR assay developed by Adler et al. [66, 85], The potency of this protein-based drug, derived from recombinant mistletoe lectine, required initial doses well below the quantification range accessible by conventional ELISA. An IPCR assay was adapted and validated for the quantification of rViscumin in standardized human serum [66, 85, 86] and subsequently... 

The inter- and intra-assay precision (% C.V.) of this method were reported to be less than 8% across the range of the limits of quantification (0.05-10 ng/ml). The accuracy (% bias) for all spiked control concentrations did not exceed 4%. Same-day turnaround of results for over 100 samples was possible and was used to support an acute dose tolerance and pharmacokinetic study that involved the analysis of 1600 samples. 

An LC-MS-MS method to study the pharmacokinetic behavior of adefovir, an antihepatitis B virus drug. Following protein precipitation the sample is analyzed on a C18 column, using a triple-quadrupole tandem mass spectrometer as detector in the positive electrospray ionization mode and PMPA as the internal standard. The method is hnear in the concentration range 0.25-100 ng/ml, with the lower hmit of quantification 0.25 ng/ml. The intra- and interday relative standard deviation over the entire concentration range is <5.7%. The accuracy determined at three concentrations is within 2.5% relative error. The method was successfully used in pharmacokinetic studies. 

Also, if conversion of drug to active metabolite shows significant departure from linear pharmacokinetics, it is possible that small differences in the rate of absorption of the parent drug (even within the 80-125% range for log transformed data) could result in clinically significant differences in the concentration/ time profiles for the active metabolite. When reliable data indicate that this situation may exist, a requirement of quantification of active metabolites in a bioequivalency study would seem to be fully justified. 

---