A rapid, specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the determination of penciclovir in human plasma. The method involved simple, one-step SPE procedure coupled with a C(18) , 75 × 4.mm, 3 µm column with a flow-rate of 0.5 mL/min, and acyclovir was used as the internal standard. The Quattro Micro mass spectrometry was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. Using 250 µL plasma, the methods were validated over the concentration range 52.555-6626.181 ng/mL, with a lower limit of quantification of 52.55 ng/mL. The intra- and inter-day precision and accuracy values were found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a clinical pharmacokinetic study in human volunteers.
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