Magnetic solid-phase extraction coupled with LC-MS/MS methods for the simple extraction and rapid determination of sugammadex in human plasma

Abstract

Sugammadex (SUG) is a novel antagonist of neuromuscular blocking agents (NMBAs). The NMBA rocuronium is usually employed to obtain better surgical conditions in kidney transplant. Nevertheless, rocuronium has several disadvantages, such as an increased risk of pulmonary complications. Thus, SUG is vital to kidney-transplant surgery. However, because SUG is excreted by the kidneys in prototypes, the pharmacokinetics (PK) may be affected in patients with renal impairment. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to monitor SUG in plasma samples to investigate the PK of SUG in kidney-transplant patients. Due to the complexity and limitation of other methods of sample preparation, magnetic solid-phase extraction (MSPE) was adopted to purify samples. Chromatographic separation was obtained using a reversed-phase Polaris® C18 column and gradient elution with 0.1% formic acid (FA) in water as phase A and in methanol (MeOH) as phase B as mobile phases. The transitions 999.7 → 963.9 (m/z) and 1055.7 → 1012.2 (m/z) were used to quantify SUG and ORG26265, respectively, under negative electrospray ionization. A linear calibration curve was achieved in concentrations varying from 100 to 10 000 ng mL⁻¹. The acceptable accuracy varied from 95.7% to 106.4%, and intra- and inter-precision did not exceed 15% (20% at the lower limit of quantitation (LLOQ)). The matrix effect, stability, dilution integrity, and carry-over were validated. This method was applied successfully for the PK study of 13 recipients and 12 donors of kidney transplant after intravenous injection of SUG (2 mL per kg bodyweight).