A small-scale method of sample preparation suitable for simultaneous HPLC-UV assay of capecitabine and its 5'-DFCR metabolite in mouse blood plasma

Abstract The objective of the study was to develop an easy, cheap, effective, and safe, small-scale method for sample preparation suitable for the simultaneous high-performance liquid chromatography (HPLC)-ultraviolet (UV) assay of capecitabine and its 5′-deoxy-5-fluorocytidine (5′-DFCR) metabolite in mouse blood plasma. The suitability of the proposed method of sample preparation was verified by the optimal effectiveness and efficiency achieved in the overall analytical workflow. The chromatographic separation of capecitabine and its first metabolite was performed on a Hypersil GOLD aQ column with a mobile phase consisting of 1% formic acid, methanol, and water, and run in a gradient elution mode. The absence of interfering endogenous components at the retention times of each analyte was confirmed by the chromatographic analysis of blank matrices and matrices spiked with the corresponding standards. The absence of any tactile matrix effect was also recorded. For the first time, the effect of the vacutainer's anticoagulant on the extraction efficiency of both analytes was evaluated. The method was found to be accurate, precise, and specific. The estimated mean "extraction" efficiencies were ≥90% for each analyte. The lower limit of quantitation for both capecitabine and 5′-DFCR was 0.05 μg/mL.

Dosage of Lipid Emulsions as an Antidote to Lipid-Soluble Substances.

INTRODUCTION: Lipid emulsions are increasingly used as an antidote to lipophilic drug intoxications. The dose recommended by the American Society of Regional Anesthesia is used primarily for the treatment of local anesthetic systemic toxicity. There is insufficient information about what the dose of lipid emulsions (LE) should be in other intoxications depending on their severity. AIM: To determine the LE dose in a shock or haemodynamic instability in patients with acute exogenous intoxications treated with LE. MATERIALS AND METHODS: Forty-nine patients with acute lipophilic drug intoxications were treated with LE in the Clinic of Toxicology at the Naval Hospital in Varna.Statistical analysis was performed using the statistical functions of Excel 2016 and the Statistica 7.0 software package. RESULTS: The percentage of patients receiving a low dose of LE of 0.3 ml/kg (93.87%) was significantly higher than the percentage of patients treated with a medium (2.04%) and a high dose (4.08%) of LF. The high dose of LE of 1.5 ml/kg recommended by the American Society of Regional Anesthesia was administered to two patients (4.08%). In severe intoxications with exotoxic shock, the rate of LE administration varies from 20 ml/h to 40 ml/h. CONCLUSIONS: In severe intoxications with cardiotoxic syndrome and haemodynamic instability, LE should be used in the dose as suggested by the American Society of Regional Anesthesia. It is possible to use lower doses of LE in the range of 0.3-0.6 ml/kg in all moderate poisonings administered by continuous intravenous infusion for 12-24-48 hours. No side effects were observed at these doses.

Current applications of plasmapheresis in clinical toxicology.

The clinical applications of plasmapheresis are rapidly increasing in number and scope. This trend is also observed in the application of plasmapheresis as a method of detoxification in clinical toxicology. Because of a lack of large controlled series, the rationale for using plasmapheresis must be confirmed in each type of intoxication by evidence of effective clearance, as well as by high plasma protein binding and a low volume of distribution of the toxic substance. Plasmapheresis is used mostly to treat phalloid mushroom intoxications. In this potentially fatal intoxication, for which there is no antidote, plasmapheresis is at least as effective as haemoperfusion in reducing mortality from as high as 30-50% with conventional therapy to <20%. In our series of 28 patients treated with plasmapheresis, mortality was 17.8%. In our experience, plasmaphe-resis is also very effective in the treatment of life-threatening intoxications with tricyclic (amitriptyline) and 4-cyclic (maprotyline) antidepressants. We confirmed a 63% reduction in the plasma level of amitriptyline in one patient after single plasmapheresis. Other drugs such as L-thyroxine, verapamil, diltiazem and carbamazepime are also removed effectively by plasmapheresis, as are theophylline and heavy metals (mercury and vanadate). Phosphoroorganic substances are not removed effectively. We measured the plasma concentrations of dimethoate in two patients with this intoxication and did not find clinically significant clearance with plasmapheresis.