Development and validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of acrivastine and pseudoephedrine in human plasma and its application in pharmacokinetics.

A specific, sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of acrivastine and pseudoephedrine in human plasma samples. Plasma samples were processed and analyzed on a Phenomenex Luna 3 µ CN 100A column (150 mm×2.0 mm) eluted with the mobile phase consisting of methanol and 0.01 mol/L ammonium acetate water solution containing 0.1% formic acid (45:55, v/v) at a flow rate of 0.2 mL/min. The analytes were detected by positive ion electrospray ionization in multiple reaction monitoring mode. The transitions of m/z 349→278, m/z 166→148 and m/z 256→167 were monitored for acrivastine, pseudoephedrine and diphenhydramine (IS), respectively. The method was specific and sensitive with a lower limit of quantitation (LLOQ) of 1.52 ng/mL for acrivastine and 8.13 ng/mL for pseudoephedrine. The method showed good linearity in the range of 1.52~606.0 0 ng/mL for acrivastine and 8.13~813.12 ng/mL for pseudoephedrine (r≥0.996). The mean recovery were ranged 91.82% ~ 98.46% for acrivastine and 90.77% ~ 92.05% for pseudoephedrine. Validation results, such as accuracy, precision and repeatability were within the required limits. The method was successfully applied in a pharmacokinetic study of the acrivastine and pseudoephedrine hydrochloride compound capsule in humans.

Dextran permeation through poly(N-isopropylacrylamide) hydrogels.

The permeation of macromolecules such as fluoroescein-labeled dextran fractions through thermally reversible hydrogels has been investigated. A permeation model has been formulated, which takes into account hydrogel porosity and tortuosity as well as the combined effect of a geometric restraint for a relatively large solute molecule at a pore entrance and the friction between solute molecules moving through the pores and pore walls. Based on this model, we have estimated the tortuosity and average pore size of a swollen hydrogel, poly(N-isopropylacrylamide) [poly(NIPAAm)] and a swollen heterogel, poly(N-isopropylacrylamide-co-vinyl-terminated dimethylsiloxane) [poly(NIPAAm-co-VTPDMS)]. The permeation data for dextran molecules up to the size of 43.5 A in radius show good agreement with the values predicted from the model.