Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring.

Therapeutic drug monitoring (TDM) is necessary for the optimal administration of anti-arrhythmic drugs in the treatment of heart arrhythmia. The present study aimed to develop and validate a direct analysis in real time tandem mass spectrometry (DART-MS/MS) method for the rapid and simultaneous determination of five anti-arrhythmic drugs (metoprolol, diltiazem, amiodarone, propafenone, and verapamil) and one metabolite (5-hydroxy(OH)-propafenone) in human serum. After the addition of isotope-labeled internal standards and protein precipitation with acetonitrile, anti-arrhythmic drugs were ionized by DART in positive mode followed by multiple reaction monitoring (MRM) detection. The use of DART-MS/MS avoided the need for chromatographic separation and allowed rapid and ultrahigh throughput analysis of anti-arrhythmic drugs in a total run time of 30 s per sample. The DART-MS/MS method yielded satisfactory linearity (R2 ≥ 0.9906), accuracy (86.1-109.9%), and precision (≤ 14.3%) with minimal effect of biological matrixes. The method was successfully applied to analyzing 30 clinical TDM samples. The relative error (RE) of the concentrations obtained by DART-MS/MS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was within ± 13%. This work highlights the potential usefulness of DART for the rapid quantitative analysis of anti-arrhythmic drugs in human serum and gives rapid feedback in the clinical TDM practices.

Treatment of displaced radial neck fractures under ultrasonographic guidance in children.

PURPOSE: This study aimed to evaluate the feasibility of reduction under ultrasonographic (US) guidance with Kirschner wires (K-wires) and fixation with elastic stable intramedullary nails (ESINs) in the treatment of radial neck fractures (RNFs). METHODS: This retrospective study included 50 children treated for Judet types III and IV RNFs at our hospital from September 2015 to November 2018. Patients were divided into two groups: group A (without US) and group B (with US). Group A patients were treated using the Métaizeau technique; one K-wire was used for reduction under the guidance of X-ray fluoroscopy. Group B patients were treated using the same technique, but under the guidance of US. Post-operative radiographs, elbow function, and complications were analyzed. RESULTS: All patients were followed up over a period of 12 months. Five patients in group A had posterior interosseous nerve (PIN) injury, whereas no patient in group B had PIN injury (p = 0.016). The use of US guidance resulted in lower radiation exposure and shorter operation time. According to the Mayo Elbow Performance Index, there was no significant difference between the two groups (p = 0.814), including post-operative complications (radial head necrosis, fracture displacement, or stiffness). CONCLUSION: US guidance during surgery is feasible to treat Judet type III and IV RNFs. US guidance can significantly reduce X-ray radiation exposure and the risk of PIN injury.

In situ calibration of Direct Analysis in Real Time-mass spectrometry for direct quantification: Urine excretion rate index creatinine as an example.

Ambient ionization in open environment brings a capability of a coupled mass spectrometry to detect target molecules in situ. However, it is limited to qualitative and semi-quantitative analysis. By coupling of an ambient ionization-based Direct Analysis in Real Time (DART) with high-resolution quadrupole time-of-flight mass spectrometry (QTOF/MS), we observe that, in one-chemical system, the target molecule displays a non-linear response in MS signal vs concentration, accompanying with large variation in MS signal, suggesting two obstacles for quantification to be overcome. Surprisingly, in a two-chemical system, we observe an apparent suppression effect. We prove that, due to this observed suppression effect, a fluctuant response in the MS signal of the stable isotope-labeled analogue can immediately reflect the change in the analyte concentration and ionization efficiency. For example, by taking advantage of this effect, even the analyte of different concentrations despairingly displayed similar signals would be accurately calibrated through the suppression of the internal stable isotope standard. This puts an important foundation on accurate and linear quantitation of analytes in complex matrix using DART-MS assay. Moreover, we for the first time demonstrate an application of in situ calibration of DART-MS for direct and accurate quantification of target molecule (creatinine) in highly complex samples (human urine) without any pre-separation. The quantification is also validated using HPLC-UV analysis (n = 38). At last, we show that stable isotope-labeled-creatinine (m/z 117.0850 amu) can be used for simultaneous in situ calibration of some other urinary metabolites with a mass/charge ratio varying from 120.069 amu to 333.125 amu.

The direct analysis of drug distribution of rotigotine-loaded microspheres from tissue sections by LESA coupled with tandem mass spectrometry.

The direct analysis of drug distribution of rotigotine-loaded microspheres (RoMS) from tissue sections by liquid extraction surface analysis (LESA) coupled with tandem mass spectrometry (MS/MS) was demonstrated. The RoMS distribution in rat tissues assessed by the ambient LESA-MS/MS approach without extensive or tedious sample pretreatment was compared with that obtained by a conventional liquid chromatography tandem mass spectrometry (LC-MS/MS) method in which organ excision and subsequent solvent extraction were commonly employed before analysis. Results obtained from the two were well correlated for a majority of the organs, such as muscle, liver, stomach, and hippocampus. The distribution of RoMS in the brain, however, was found to be mainly focused in the hippocampus and striatum regions as shown by the LESA-imaged profiles. The LESA approach we developed is sensitive enough, with an estimated LLOQ at 0.05 ng/mL of rotigotine in brain tissue, and information-rich with minimal sample preparation, suitable, and promising in assisting the development of new drug delivery systems for controlled drug release and protection. Graphical abstract Workflow for the LESA-MS/MS imaging of brain tissue section after intramuscular RoMS administration.