Determination of pipothiazine in human plasma by reversed-phase high-performance liquid chromatography.

A method is described for the determination of pipothiazine in human plasma, based on reversed-phase HPLC. The method has been applied in a pharmacokinetic study of pipothiazine in six psychiatric patients receiving repeated depot intramuscular injections for six months. A number of compounds likely to be taken concurrently by patients were tested for potential to interfere with the assay. There was no evidence of "dose-dumping" in the period following injection. Comparison of the pharmacokinetic profiles after the first and sixth injections showed no evidence of drug accumulation.

Caffeine as a potential indicator for acetylator status.

The identification of patients as 'fast acetylators' or 'slow acetylators' is used in clinical practice to help recognize those at risk from toxicity and in guiding the dosage of N-acetylated drugs. Caffeine has been proposed as a marker for drug acetylation on the basis of a ratio of urinary metabolites (5-acetylamino-6-formylamino-3-methyl uracil and 1-methylxanthine, AFMU:MX) determined by high-performance liquid chromatography. The caffeine test was studied in 26 subjects by reference to the use of sulphamidine as the test substance. The distribution of urinary AFMU:MX ratios allowed assignment of subjects to 'slow' and 'fast' acetylator status (AFMU:MX less than 2.1 and greater than 2.3 respectively). The results showed accordance with those from the sulphadimidine test with the exception of one subject. The possible interference of concurrent administration of sulphadimidine (as an example of a drug known to undergo metabolism by N-acetylation) was also studied in 11 of the subjects. The interference was found to be small (apparent mean bias 11%) but of possible clinical significance.

A visual assay to monitor purification of cell surface antigens reacting with monoclonal antibodies.

We have developed a visual microtiter assay to detect solubilized cell-surface antigens which react with monoclonal antibodies. The assay depends on the ability of adsorbed monoclonal antibody to bind target cells to microtiter V wells, and the inhibition of binding by antigen. We have used this assay to follow a 600-fold purification of the human lymphocyte differentiation antigen 3A1 extracted from HSB-2 cells. Antigen 3A1 is a glycoprotein with a molecular weight of approximately 40,000 daltons.