Easy and fast LC-MS/MS determination of lidocaine and MEGX in plasma for therapeutic drug monitoring in neonates with seizures.

A fast liquid chromatography-tandem mass spectrometry with electrospray ionization method was developed and validated for simultaneous quantification of lidocaine and its active metabolite MEGX in 10 µL of plasma of neonates with seizures. The sample preparation consists of an easy protein precipitation sample pre-treatment with methanol. Chromatographic separation was achieved on a Alltima HP C18-EPS 150 mm×2.1mm column with an isocratic mobile phase of 0.1% (v/v) ammonium acetate in purified water-0.1% (v/v) formic acid in acetonitrile (70:30, v/v). The analytes were detected with a Thermo Scientific triple quadrupole Quantum Access with positive ionization. Ions monitored in the selected reaction monitoring (SRM) mode were m/z 235.2→86.6 for lidocaine (at 3.35 min), m/z 207.1→58.8 for MEGX (at 2.75 min) and 280.1→86.7 for 3-nitrolidocaine (internal standard, at 3.20 min). The method was validated over a linear range of 0.2-18.0mg/L for lidocaine and MEGX, using 3-nitrolidocaine as the internal standard. The lower limit of quantification (LLQ) was 0.2mg/L for lidocaine and MEGX. The within-run and between-run CV (%) were lower than 6.9% for both lidocaine and MEGX. Recoveries were in the range of 99.4% to 103.6%. Observed LC-MS/MS matrix effects were -6.2% for MEGX (ion suppression) and were negligible for lidocaine and the internal standard (i.e. <0.1%). Compared to other bioanalytical articles published in medical literature (PubMed) during the last 15 years that described LC-MS/MS methods for quantification of lidocaine in human plasma, our method uses less plasma, has a shorter and more simple sample pre-treatment and has a short run time.

Propofol and thiopental for refractory status epilepticus in children.

To assess safety and efficacy of propofol and thiopental for refractory status epilepticus (RSE) in children, the authors reviewed 34 episodes of RSE. Thiopental was effective in most patients, but there were serious side effects. Propofol was used according to a strict protocol. It was effective in most patients, so that thiopental was not needed. Side effects were infrequent, of minor severity, and fully reversible. The authors suggest the use of propofol before thiopental.

Phenytoin sodium as a treatment for ventricular dysrhythmia in horses.

Five adult horses with ventricular extra systoles (VES) and 2 with ventricular tachycardia (VT) refractory to treatment with rest, anti-inflammatory drugs, lidocaine, or procainamide were treated with phenytoin sodium p.o. q12h. The starting dosage of phenytoin was 20 or 22 mg/kg body weight (BW) q12h, and the maintenance dosage varied from 8 to 17 mg/kg BW q12h. The mean +/- standard deviation therapeutic blood concentration of total phenytoin was 8.8 +/- 2.1 mg/L, and the mean concentration of free phenytoin of 2.5 +/- 0.5 mg/L was relatively constant at a range of 24 to 29% of the total phenytoin concentration. In all horses, both VES and VT were abolished after treatment with phenytoin. On the basis of the results of this clinical study, the authors propose an initial dose of 20 mg/kg BW q12h for the first 3 or 4 dosages, followed by a maintenance dose of 10 to 15 mg/kg BW q12h. Phenytoin plasma concentrations should be monitored during therapy. High plasma concentrations were associated with adverse effects such as recumbency and excitement. In this study, which included a limited number of diverse patients, phenytoin sodium appeared to be an inexpensive and effective treatment for persistent VES or VT in cases where conventional treatment had failed.