Determination of aspirin and its major metabolites in plasma by high-performance liquid chromatography without solvent extraction.

Compressed and enteric-coated acetylsalicylate (ASA) tablets have been compared in normal healthy subjects. Plasma ASA and salicylate (SA) were measured by high pressure liquid chromatography (HPLC). Platelet cyclooxygenase activity in vitro was studied by a radiometric technique. Following ingestion of 650 mg of ASA in the form of compressed tablets, cyclooxygenase activity was inhibited 95% within 45 min. Enzyme activity was observed to increase within 8 h and reached 10% of control level by 24 h. The pattern suggests that only circulating platelets are affected by ASA ingestion. Following the administration of 650 mg of ASA as enteric-coated tablets comparable inhibition of cyclooxygenase activity was observed, although the effect was delayed, reflecting the delayed appearance of ASA in the plasma. Return to control levels followed a pattern similar to that observed with the compressed tablet.

Plasma acetylsalicylate and salicylate and platelet cyclooxygenase activity following plain and enteric-coated aspirin.

HPLC (high-performance liquid chromatography) is an analytical method of great versatility and sensitivity. The use of silica-bonded non-polar stationary phases in place of the traditional polar stationary phases has resulted in the technique of reversed-phase chromatography. This has proved a most useful analytical tool, particularly for the analysis of biological samples. Furthermore the technique has great potential as a means of measuring a number of physicochemical properties.

Reversed-phase chromatography

Objective: Although water-soluble drugs can be removed by haemofiltration/haemodialysis, morbidity and mortality from intoxication with protein-bound drugs remains high. The present study investigates whether albumin dialysis in the form of the Molecular Adsorbents Recirculating System (MARS) is effective in removal of protein-bound drugs. Design: Prospective animal study. Setting: Surgical research laboratory in a university hospital. Subjects: Seven female Norwegian Landrace pigs. Intervention: We studied whether midazolam (97% albumin-bound) and fentanyl (85% alpha-1-acid glycoprotein-bound), administered as anaesthetics to pigs with induced acute liver failure, could be removed by MARS dialysis lasting for 4 h. Measurements: After 4 h of dialysis, total and free anaesthetic concentrations were measured in the blood and dialysate from different segments of the MARS circuit. Main results: Midazolam: total plasma concentrations fell by 47.1±2.1% (in 4 h) across the MARS filter (p<0.01). The charcoal component of the system reduced the total dialysate drug concentration by 16.4±2.2% (p<0.05). Free midazolam removal followed a similar pattern. Fentanyl: total plasma concentrations fell by 56.1±2.4% (in 4 h) across the MARS filter (p<0.01). Clearance of fentanyl from the dialysate by the charcoal was 70±0.7% at 4 h (p<0.001). Conclusions: The results of the study show that MARS can remove both albumin and other protein-bound drugs efficiently from the plasma, and it may have a place for the treatment of patients suffering from intoxication with this class of compounds.

/pdf/albumin-dialysis-a-new-therapeutic-strategy-for-intoxication-2ve1lrwhvh.pdf

Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs.

Context. Despite a worldwide decline in barbiturate use, cases of acute poisoning with severe toxicity are still noted, particularly in developing countries. Severe poisonings often require prolonged admission to an intensive care unit, so enhanced elimination might be useful to hasten recovery. Information regarding the efficacy of these techniques for individual barbiturates is not available in standard textbooks. Objective. To determine the evidence supporting the effect of enhanced elimination and its role in the management of acute barbiturate poisoning. Methods. A systematic review was conducted using broad search criteria in three databases. All potentially relevant articles were obtained, and reference lists were manually reviewed. Ninety-four publications fulfilling inclusion criteria were located. Studies were classified as controlled or uncontrolled, and clinical and pharmacokinetic end points were manually extracted. If not directly stated, standard pharmacokinetic methods were used to calcula...

Enhanced elimination in acute barbiturate poisoning - a systematic review.

We report a specific and sensitive quantitative assay for salicylate in serum or plasma. As little as 3 microliter of sample can be analyzed by an external standard procedure and larger volumes by diluting with the internal standard (o-methoxybenzoic acid). No extraction or derivatization is necessary and salicylic acid and the internal standard elute in 6 and 3.75 min, respectively. Peak-height ratios are linearly related to concentrations between 10 and 500 mg/liter. By comparison with an existing fluorometric method, our procedure is faster, more specific, and more sensitive.

Analysis for salicylic acid in serum by high-performance liquid chromatography.

We examined the efficacy of a new, fixed-bed, uncoated charcoal device in experimentally intoxicated dogs and in drug-intoxicated as well as chemically poisoned patients. In the animal studies, 4 h of hemoperfusion resulted in a significant decrease in the blood level of phenobarbital, salicylate, pentobarbital and glutethimide. The drug clearances varied between 97 ± 10 and 129 ± 6 ml/min. However, the total amount of drug removed was higher for phenobarbital and salicylate which have a small apparent volume of distribution (AVD) than for pentobarbital and glutethimide which have an AVD greater than total body water. We next treated 14 patients suffering from a wide variety of intoxications. Patients intoxicated with phenobarbital, methsuximide, chlordane and Amanita muscaria all showed a significant improvement in their clinical status. Patients intoxicated with ethchlorvynol, glutethimide, methaqualone, podophylhn and fluoroacetamide did not improve. Charcoal hemoperfusion may be useful in patients poisoned with drugs characterized by an AVD smaller than total body water. No major complications were encountered during the hemoperfusions.

Fixed-bed uncoated charcoal hemoperfusion in the treatment of intoxications: animal and patient studies.

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Analysis for salicylic acid in serum by high-performance liquid chromatography.

Fixed-bed uncoated charcoal hemoperfusion in the treatment of intoxications: animal and patient studies.