Hydrophilic interaction liquid chromatography/positive ion electrospray ionization mass spectrometry method for the quantification of perindopril and its main metabolite in human plasma.

A validated method based on liquid chromatography/positive ion electrospray-mass spectrometry (LC-ESI/MS) is described for the quantification of perindopril and its active metabolite, perindoprilat, in human plasma. The assay was based on 500-microL plasma samples, following solid-phase extraction using Oasis HLB cartridges. All analytes and the internal standard (trandolapril) were separated by hydrophilic interaction liquid chromatography using a SeQuant Zic-HILIC analytical column (150.0 x 2.1 mm i.d., particle size 3.5 microm, 200 A) with isocratic elution. The mobile phase consisted of 10% 5.0 mM ammonium acetate water solution in a binary mixture of acetonitrile/methanol (60:40, v/v) and pumped at a flow rate of 0.10 mL min(-1). Quantitation of the analytes was performed with selected ion monitoring (SIM) in positive ionization mode using electrospray ionization interface. The assay was found to be linear in the concentration range of 5.0-500.0 ng mL(-1) for perindopril and perindoprilat. Intermediate precision were found less than 3.5% over the tested concentration ranges. A run time of less than 6.0 min for each sample made it possible to analyze a large number of human plasma samples per day. The method is the first reported application of HILIC in the analysis of angiotensin-converting enzyme inhibitors and can be used to quantify perindopril and perindoprilat in human plasma covering a variety of pharmacokinetic or bioequivalence studies.

Selective and rapid liquid chromatography/negative-ion electrospray ionization mass spectrometry method for the quantification of valacyclovir and its metabolite in human plasma.

A rapid, sensitive and specific method was developed for the quantification of valacyclovir and acyclovir in human plasma. Sample preparation was performed by protein precipitation with acetonitrile followed by filtration. Valacyclovir, acyclovir and ganciclovir (internal standard) were separated isocratically on a reversed-phase porous graphitized carbon analytical column (2.1 mm x 125.0 mm i.d., particle size 5 microm), using a mobile phase of acetonitrile/water with 0.05% (v/v) diethylamine (50:50, v/v) at a flow rate of 0.15 mL min(-1) in 4.0 min. Detection was performed by negative electrospray ionization using the selected ion monitoring mode of the deprotonated molecular ions at m/z 323.0 for valacyclovir, 224.0 for acyclovir and 254.0 for ganciclovir. The assay had linear calibration curves over the range 0.020-0.800 microg mL(-1) for valacyclovir and 0.100-20.00 microg mL(-1) for acyclovir. Accuracy and precision were within the acceptance limit of 15%. The method was successfully applied to the analysis of plasma samples obtained from patients after oral administration of valacyclovir.