Determination of duloxetine in human plasma via LC/MS and subsequent application to a pharmacokinetic study in healthy Chinese volunteers

Abstract

Background The pharmacokinetics of duloxetine hydrochloride have been well studied after its approval for clinical use. However, few such data have been reported in the English language literature. We developed a method to determine the pharmacokinetics of duloxetine enteric-coated capsules in healthy Chinese volunteers. Methods A rapid and sensitive liquid chromatography–mass spectrometric (LC/MS) method for the determination of duloxetine in human plasma using flupentixol as the internal standard (I.S.) was developed and validated. Sample preparation of the plasma involved deproteination with acetonitrile twice, repeatedly. Samples were then analyzed by HPLC on a Thermo Hypersil–Hypurity C18 column (150 × 2.1 mm, 5 μm). A single–quadrupole mass spectrometer with an electrospray interface was operated in the selected-ion monitoring mode to detect the [M + H] + ions at 298 m/z for duloxetine and at 435 m/z for the internal standard. Results Pharmacokinetics were measured in 12 healthy Chinese male volunteers (6 males and 6 females) who received a single regimen with 3 different dosages at 22.4, 44.8 and 67.2 mg of duloxetine enteric-coated capsules. Conclusion A sensitive and specific method for quantifying duloxetine levels in human plasma has been devised and successfully applied to a clinic pharmacokinetic study of an enteric-coated capsule of duloxetine hydrochloride administered as a single oral dose.