A novel LC-MS/MS method for the quantification of ulipristal acetate in human plasma: Application to a pharmacokinetic study in healthy Chinese female subjects.

Abstract

A LC-MS/MS method for the detection of ulipristal acetate in humans which was not only simple and rapid in sample pretreatment process and chromatographic condition, but also highly selective and sensitive in MS condition was developed, and the fully validated method was applied for investigating the pharmacokinetic properties of ulipristal acetate following single oral administration of Esmya in healthy Chinese subjects for the first time. After single-step protein precipitation with methanol, ulipristal acetate and ulipristal acetate-d3 (IS) were chromatographed on an ACE Excel 3 C18-PFP column with gradient elution procedure, and detected by positive electrospray ionization with multiple reaction monitoring mode using the respective precursor-product ion transitions of m/z 476.2→134.1 for ulipristal acetate and m/z 479.3→416.2 for IS. The assay has desirable accuracy and precision over a wide linear range of 0.0500 - 100 ng/mL for ulipristal acetate, and no interference caused by endogenous compounds was detected. It also exhibits satisfactory matrix effect, extraction recovery, and stability. Cmax of ulipristal acetate after oral administration of a single 5-mg dose of 47.7 ± 27.7 ng/mL was detected at 0.91 ± 0.98 h (tmax) with AUC0-t of 112 ± 49 ng·h/mL. Ulipristal acetate was eliminated slowly with T1/2 of 46.4 ± 14.0 h. The major advantages of the current approach involve one-step precipitation of plasma protein with methanol, high selectivity with a lower limit of quantitation of 0.0500 ng/mL, small plasma volume of 50 µL for processing and a short run time of 4 min per sample, which allow its applicability for a pharmacokinetic study in healthy Chinese subjects.