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We report on a surface-enhanced Raman scattering (SERS) platform for the detection of five beta-blockers (β-blockers): atenolol, esmolol, labetalol, sotalol, and propranolol. Key to this platform was a two-dimensional substrate formed by self-assembling large Ag@SiO 2 nanoparticles (Ag@SiO 2 NPs) on a silicon wafer. The close arrangement of these large nanoparticles on the surface generated a strong and uniform electromagnetic field, which enhanced SERS signal intensity for the detection of small amounts of the target molecules. The intensities of characteristic peaks of the five β-blocker drugs increased linearly with the increase of their concentrations in the range of 10 -5 to 10 -8 mol/L. The detection limits were 10 -10 mol/L for propranolol, 10 -9 mol/L for atenolol, labetalol, and sotalol, and 10 -8 mol/L for esmolol. Determination of these five β-blocker drugs added to human urine samples, using a portable Raman spectroscopy instrument, showed quantitative recovery (93-101%). Principal component analysis (PCA) and hierarchical cluster analysis (HCA) of SERS spectral data improved the differentiation among these five β-blockers. This study highlights the potential of the developed SERS platform for rapid, on-site detection of illicit drugs and for antidoping screening.

Most contemporary methods of screening and quantitating controlled substances and therapeutic drugs in biofluids typically require laborious, time-consuming, and expensive analytical workflows. In recent years, our group has worked toward developing microextraction (μe)-mass spectrometry (MS) technologies that merge all of the tedious steps of the classical methods into a simple, efficient, and low-cost methodology. Unquestionably, the automation of these technologies allows for faster sample throughput, greater reproducibility, and radically reduced analysis times. Coated blade spray (CBS) is a μe technology engineered for extracting/enriching analytes of interest in complex matrices, and it can be directly coupled with MS instruments to achieve efficient screening and quantitative analysis. In this study, we introduced CBS as a technology that can be arranged to perform either rapid diagnostics (single vial) or the high-throughput (96-well plate) analysis of biofluids. Furthermore, we demonstrate that performing 96-CBS extractions at the same time allows the total analysis time to be reduced to less than 55 s per sample. Aiming to validate the versatility of CBS, substances comprising a broad range of molecular weights, moieties, protein binding, and polarities were selected. Thus, the high-throughput (HT)-CBS technology was used for the concomitant quantitation of 18 compounds (mixture of anabolics, β-2 agonists, diuretics, stimulants, narcotics, and β-blockers) spiked in human urine and plasma samples. Excellent precision (∼2.5%), accuracy (≥90%), and linearity (R 2 ≥ 0.99) were attained for all the studied compounds, and the limits of quantitation (LOQs) were within the range of 0.1 to 10 ng·mL -1 for plasma and 0.25 to 10 ng·mL -1 for urine. The results reported in this paper confirm CBS's great potential for achieving subsixty-second analyses of target compounds in a broad range of fields such as those related to clinical diagnosis, food, the environment, and forensics.

The technique of automated in-tube solid-phase microextraction (SPME) coupled with liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) was evaluated for the determination of beta-blockers in urine and serum samples. In-tube SPME is an extraction technique for organic compounds in aqueous samples, in which analytes are extracted from the sample directly into an open tubular capillary by repeated draw/eject cycles of sample solution. LC/MS analyses of beta-blockers were initially performed by liquid injection onto a LC column. Nine beta-blockers tested in this study gave very simple ESI mass spectra, and strong signals corresponding to [M + H]+ were observed for all beta-blockers. The beta-blockers were separated with a Hypersil BDS C18 column using acetonitrile/methanol/water/acetic acid (15:15:70:1) as a mobile phase. To optimize the extraction of beta-blockers, several in-tube SPME parameters were examined. The optimum extraction conditions were 15 draw/eject cycles of 30 microL of sample in 100 mM Tris-HCl (pH 8.5) at a flow rate of 100 microL/min using an Omegawax 250 capillary (Supelco, Bellefonte, PA). The beta-blockers extracted by the capillary were easily desorbed by mobile-phase flow, and carryover of beta-blockers was not observed. Using in-tube SPME/LC/ESI-MS with selected ion monitoring, the calibration curves of beta-blockers were linear in the range from 2 to 100 ng/mL with correlation coefficients above 0.9982 (n = 18) and detection limits (S/N = 3) of 0.1-1.2 ng/mL. This method was successfully applied to the analysis of biological samples without interference peaks. The recoveries of beta-blockers spiked into human urine and serum samples were above 84 and 71%, respectively. A serum sample from a patient administrated propranolol was analyzed using this method and both propranolol and its metabolites were detected.

Several beta-antagonists (acebutolol, atenolol, celiprolol, labetalol, metoprolol, nadolol, propranolol) were determined in urine samples with fluorometric detection after direct injection, in less than 15 min, with a micellar mobile phase of 0.1 M sodium dodecyl sulfate (SDS), 15% propanol, and 1% triethylamine at pH 3. The limits of detection (38 criterion) were usually between 3 and 30 ng/mL. The addition of propanol and triethylamine and the reduction of the pH of the mobile phase improved the efficiency of the chromatographic peaks that was rather low in pure micellar eluents. The selection of the composition of the mobile phase was easily performed through the use of an interpretive procedure which considered the retention times and peak shapes of the beta-antagonists in six chromatograms, obtained at varying concentrations of SDS (0.05-0.15 M) and propanol (5-15% v/v). The chromatograms of urine samples from healthy volunteers, which were administered atenolol, metoprolol, and propranolol, showed only one peak for the former drug and several peaks for the other two. These peaks corresponded to the parent drug and metabolites, which indicated the partial and the extensive degradation of metoprolol and propranolol, respectively.