Quantitation using HRMS: A new tool for rapid, specific and sensitive determination of catecholamines and deconjugated methanephrines metanephrines in urine.

Urinary catecholamines and their methylated metabolites are biochemical indicators of pheochromocytoma, paraganglioma and neuroblastoma. A rapid and precise analytical method based on solid-phase extraction (SPE) and liquid chromatography separation coupled to high-resolution mass spectrometry (LC-HRMS) was developed and validated to measure urinary catecholamines (epinephrine (E), norepinephrine (NorE), dopamine (D)) and total methylated metabolites (normetanephrine (NorMN), metanephrine(MN) and 3-methoxytyramine (3-MT)) in a clinical setting. Results of 51 urine specimens measured using this LC-HRMS method were compared with a liquid chromatography assay with electrochemical detection (LC-EC). Urine samples (200 µL) were spiked with an internal standard solution followed by SPE purification. In the case of total methylated metabolites, urine was hydrolyzed before SPE purification. Separation was achieved on an Acclaim Mixed Mode WCX column, with an 8.5 min runtime. All compounds were detected in electrospray positive ionization mode with a parallel reaction monitoring acquisition and quantified with a linear regression (r2 > 0.998) between 2 and 200 µg/L (10.9-1090; 11.8-1182 nmol/L) for E and NorE respectively and between 10 and 1000 µg/L for others (65.2-6520; 50.7-5070; 54.5-5450 ; 59.8-5980 nmol/L for D, M, NorMN and 3-MT, respectively). Overall imprecision and bias did not exceed 15%. No significant matrix effect was observed. Correlation between the two assays was good except for epinephrine. Epinephrine concentrations measured by LC-EC method were slightly higher than values obtained with LC-HRMS method but without impact on clinical decision. This LC-HRMS assay provides a new tool for simultaneous quantitative catecholamine determination and was successfully applied in routine for the screening or follow up of pheochromocytoma, paraganglioma and neuroblastoma. LC-HRMS method offers significant advantages compared to LC-EC with good sensitivity, an unambiguous analyte determination and high sample throughput.

A simple ultra-high-performance liquid chromatography-high resolution mass spectrometry assay for the simultaneous quantification of 15 antibiotics in plasma.

Antibiotic (ATB) treatment of critically ill patients with pathophysiological injuries remains a challenge due to the constant increase in antimicrobial resistance. Therapeutic drug monitoring (TDM) is advised for ATB dose adjustments to avoid suboptimal concentrations and dose-related adverse effects. Therefore, a single and reliable analytical method for a broad selection of ATBs was developed using a high-resolution mass spectrometry (HRMS) platform for frequent use in intensive care units. An UHPLC assay coupled to high resolution accurate mass acquisition has been developed for the quantification of penicillins (amoxicillin, oxacillin, piperacillin, and ticarcillin), cephalosporines (cefepime, cefotaxime, ceftazidime, and ceftriaxone), carbapenems (ertapenem, imipenem, and meropenem), lincosamide (clindamycin), quinolones (ofloxacin and ciprofloxacin) and tazobactam. Plasma samples (100µL) were spiked with an internal standard solution followed by protein precipitation. Separation was achieved on an Accucore C18 column, which enabled sample analysis every 9min. All compounds were detected in electrospray positive ion mode and quantified with a linear regression between 0.5 and 32mg/L (r2>0.998). Overall precision and accuracy did not exceed 15%. No significant matrix effect was observed for the studied ATBs. Stored stock solutions at -20°C were stable for 6 months, except for amoxicillin and imipenem. Analytes in plasma were stable for 24h under ambient conditions as well as in post-preparation in an autosampler, except for amoxicillin and imipenem. This HRMS assay provides the simultaneous quantification of 15 ATB; it fulfills the usual quality criteria and was successfully applied for routine TDM of ATBs. The method is based on a full scan acquisition, and it would be easy to add other compounds to the present panel in the future, as this assay has already been proven to be efficient for different classes of compounds.

[Early diagnosis of postinfarction ventricular aneurysm. Value of contrast scintigraphy]. / Le diagnostic précoce de l'anévrysme ventriculaire post-infarctus. Intérêt de la scintigraphie de contraste.

Early diagnosis of a ventricular aneurysm after myocardial infarction may provide a valuable means of preventing certain complications. We studied 55 patients with acute myocardial infarction on the 8th day by Technetium 99 angioscintigraphy with study of wall motion and ejection fraction at equilibrium. The results were compared with left ventriculography performed three months after infarction. Angioscintigraphy demonstrated 17 cases of dyskinesia, 16 cases of hypokinesia, and 22 cases of akinesia, divided into two subgroups depending on whether the ejection fraction was lower (n = 11) or higher than 40% (n = 11). Contrast angiography at 3 months confirmed the presence of 27 aneurysms, 17 akinetic plaques and 11 cases of hypokinesia. Comparison between the two series of investigations showed excellent correlations: in the group of dyskinesia (17 cases) an aneurysm was confirmed in 15 cases; in the group of hypokinesia (16 cases) only one aneurysm was demonstrated by the reference angiography. The results were less uniform in the group with akinesia. In the subgroup with a low ejection fraction, 9 out of 11 cases progressed to aneurysm and, in retrospect, should be considered as likely aneurysms. There were only 2 aneurysms (2/11) in the subgroup with localised akinesia and a high ejection fraction. The overall results suggest that angioscintigraphy at the 8th day of myocardial infarction is a reliable means of detecting left ventricular aneurysm; in cases of dyskinesia or widespread akinesia with an ejection fraction of less than 40% the presence of an aneurysm was confirmed in 24 out of 28 patients (86%).(ABSTRACT TRUNCATED AT 250 WORDS)