Direct doping analysis of beta-blocker drugs from urinary samples by on-line molecularly imprinted solid-phase extraction coupled to liquid chromatography/mass spectrometry

Abstract

The use of beta-blockers to enhance performance in some sports is forbidden. Based on this regulation, there is a demand for dynamic analytical procedures for analyzing these compounds quickly and without manual sample preparation. Therefore, the use of a molecularly imprinted polymer (MIP) in a multidimensional liquid chromatographic system coupled to a mass spectrometer provides a good alternative for improving the selectivity and practicality of the beta-blocker analyses, as described in this paper. A water-compatible MIP for oxprenolol was synthesized by the precipitation method, using methacrylic acid as a functional monomer and 2-hydroxyethyl methacrylate and glycerol dimethacrylate as hydrophilic monomers. A column filled with MIP was coupled to an LC-MS/MS instrument under the multidimensional configuration, with 10.0 mmol L(-1) ammonium formate buffer (pH 5.0) as the loading and reconditioning mobile phase and a 0.01% formic acid aqueous solution-methanol (30 : 70 v : v) as the elution mobile phase. The system was used for on-line extraction and quantization of oxprenolol (from 1.0 to 75.0 μg L(-1)), atenolol, propranolol, nadolol, pindolol, labetalol and metoprolol (all from 3.0 to 50 μg L(-1)) simultaneously, from urine samples. The correlation coefficient was higher than 0.99 for all the analytes. Suitable precision and accuracy were obtained.

Development of a multi‐functional concurrent assay using weak cation‐exchange solid‐phase extraction (WCX‐SPE) and reconstitution with a diluted sample aliquot for anti‐doping analysis

“…Liquid chromatography/tandem mass spectrometry (LC/MS/MS) is now extensively utilized due to its high selectivity and sensitivity. In addition, many doping analyses are conducted using various extraction methodologies, such as liquid–liquid extraction (LLE), protein precipitation (PP), or solid‐phase extraction (SPE) . SPE presents several advantages over LLE or PP because it includes a relatively simple pre‐treatment procedure and is less dependent on the proficiency of the researcher.…”

Annual banned‐substance review: analytical approaches in human sports drug testing

“…Using comprehensive and largely LC‐MS/MS‐based initial testing procedures, the detection of beta‐blockers has not been considered a major issue in sports drug testing lately; nevertheless, a simple on‐line molecular‐imprinted polymer (MIP)‐supported extraction with subsequent LC‐MS/MS analysis was shown to facilitate the detection of a subset of 7 beta‐blockers from human urine. LODs were reported between 1 and 3 ng/mL, representing a competitive approach albeit specifically designed for beta‐blockers only . The in vitro metabolism of a new drug candidate of this class of therapeutics, termed TJ0711, was presented by Hu et al .…”

“…LODs were reported between 1 and 3 ng/mL, representing a competitive approach albeit specifically designed for beta-blockers only. [226] The in vitro metabolism of a new drug candidate of this class of therapeutics, termed TJ0711, was presented by Hu et al A total of 34 metabolic products was observed, some of which might be useful for future in vivo data interpretation and, possibly, doping controls. [227]…”

Preparation of magnetic molecularly imprinted polymer for dispersive solid‐phase extraction of valsartan and its determination by high‐performance liquid chromatography: Box‐Behnken design

“…Therefore, many antihypertensive drugs were made to manage hypertension and mainly used for managing hypertension and other disorders like heart failure, myocardial infarction, and diabetic nephropathyare angiotensin II receptor [1]. They can be used alone, or together with diuretics, angiotensin-converting enzyme (ACE) inhibitors [2][3][4], beta blockers [5], or calcium channel blockers [6]. It is believed that they are the suitable alternative for the traditional inhibitors of ACE, because of their ability to selectively block the angiotensin 1 receptor in the renin-angiotensin system [7].…”