Determination of phosphonoformic acid in human plasma and urine by high-performance liquid chromatography with electrochemical detection.

Trisodium phosphonoformate (foscarnet) is used in the treatment of cytomegalovirus infections in immunocompromised patients, such as bone marrow and renal transplant recipients, as well as patients with the acquired immune deficiency syndrome. A simple high-performance liquid chromatographic assay is described using an electrochemical detector. The method is accurate, precise and reproducible. Hydrochlorothiazide is used as the internal standard. This assay allows measurement of foscarnet in biological fluids at concentrations as low as 33 microM. This method is being used for the analysis of samples in clinical trials and is important in the evaluation of the pharmacokinetic disposition of the drug.

Screening procedure for stimulant laxatives in urine using high-performance liquid chromatography with diode array detection.

We describe a liquid chromatographic screening procedure for the detection of stimulant laxatives in urine. A 2-ml urine sample was incubated with 500 U of beta-glucuronidase for 2 h at 60 degrees C. The sample was acidified with sodium acetate (pH 5.0) and extracted with 5 ml of an isopropanol-chloroform (1:9) mixture. The organic layer was cleaned up further by washing with 5 ml disodium hydrogen-phosphate (pH 7.5) before being transferred to a conical tube and evaporated to dryness. The residue was reconstituted in 100 microliters mobile phase and 3 microliters were injected onto a Hewlett-Packard Hypersil ODS (5 microns) column. The ultraviolet absorbance of the eluent was monitored at 225 nm. Rhein, bisacodyl diphenol, bisoxatin diphenol, phenolphthalein, bisacodyl, bisoxatin and danthron all eluted within 6 min. The screen was evaluated using urine specimens obtained from 19 patients who claimed they had taken one or more of the laxatives under consideration within the past 48 h. Only two patients who claimed to have taken Coloxyl and Danthron showed negative results. Eighteen of twenty laxatives (90%) taken by the patients were detected and their identity verified by plotting post-run ultraviolet spectra. We therefore conclude that the screen is sufficiently reliable to be of help in the early detection of surreptitious abusers of stimulant laxatives.

Studies on laxatives: biliary and urinary excretion in rats given danthron by intravenous infusion or gastric intubation.

Rats were infused with danthron (I) at doses of 0.48, 2.2 and 5.8 mumol/100 g body weight, or given 12 mumol/100 g with gastric tube. TLC of bile and urine demonstrated a number of metabolites, at both administration routes. These included I monosulphate (II) and -glucuronide (III), two other phase 2 metabolites which behaved as the corresponding diconjugates, and several phase 1 metabolites (IV) in conjugated form. IV as a group were estimated by photometry of hydrolysed samples, using I as a reference. Danthron conjugates as a group were determined in such samples by a specific method for I. Moreover, II and III were determined individually in unhydrolysed specimens. Following infusion, about 80% of the danthron conjugates in bile were excreted after 1 hour; the dose fractions found after 5 hours represented about 20%, 30%, and 40% at the low, intermediate and high dose level, respectively. The corresponding fractions in urine were 16%, 12% and 10%, giving rise to bile:urine excretion ratios of 1.3, 2.7 and 4.0, respectively. This change in excretion pattern was associated with changes in metabolite muster, which involved a decrease in the balance of IV:I conjugates, as well as an increase in III:II ratio. IV was more abundantly present in bile than in urine, and showed a more sustained excretion than the I conjugates. By intragastric administration, the cumulated excretion (bile + urine) of I conjugates were only 6%, 8% and 5% of dose, in three consecutive 6 hours' periods (0-6, 6-12 and 12-18 hours after dosing). The bile:urine excretion ratios seemed to decrease with time, as did the III:II ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Experience with a screening method for laxative abuse.

1 Abuse of laxatives may lead to a variety of serious disorders which are usually difficult to recognize because of the heterogenicity of the toxic effects. 2 In order to facilitate the diagnosis of chronic laxative poisoning, a laboratory screening method for the detection of colonic stimulants in urine has been designed and has been applied in practice over a three-year-period. 3 During this period, 157 samples from 81 patients were sent to the laboratory. Fifteen patients (18.5%) were definitely shown to use self-prescribed laxatives. 4 Next to the diphenolic compounds: bisacodyl, phenolphthalein and bisoxatin, the anthraquinone derivative rhein, a metabolite of vegetable laxatives, was found in several cases. In the urine of three patients a substance resembling rhein was found, which was shown to be aloe-emodin. 5 It is concluded that chronic self-poisoning with laxatives is a fairly common disorder than can easily be overlooked. Laboratory screening of the urine of suspected patients is an economic and reliable method for its diagnosis.

A screening method for establishing laxative abuse.

Abuse of laxatives, most of them belonging to the group of colonic stimulants or cathartics, can cause various disorders. Extensive diagnostic work can be avoided by early toxicological screening of the suspected patients with respect to laxatives. Because no screening method of this kind was available, we developed a procedure with which all phenolic and anthraquinone laxatives--except sodium picosulfate--can be detected in urine. This method is based on high-performance thin-layer chromatography in two systems after pretreatment of a 20-mL urine sample with beta-glucuronidase and subsequent column extraction. The procedure is very sensitive: at least 32 h after a single dose of bisacodyl, danthron, phenolphthalein, or sennoside, the drug can be detected in the urine. Bisoxatin and oxyphenisatin are still detectable in the urine 18 h after intake. The method is also highly specific; none of 73 other drugs interfered in either of the two chromatographic systems. This procedure can be helpful for the early diagnosis of laxative abuse.

Qualitative and quantitative analysis of some synthetic, chemically acting laxatives in urine by gas chromatography-mass spectrometry.

A method for the qualitative and quantitative simultaneous analysis of dioxyanthraquinone, desacetyl-Bisacodyl, phenolphthalein and Oxyphenisatin in human urine using gas chromatography-mass spectrometry (GC-MS) has been developed. The compounds were extracted from urine at pH 7.5 with diethyl ether using Extrelut extraction columns, followed by evaporation and trimethylsilylation. The method used electron beam ionization GC-MS employing a computer-controlled multiple-ion detector (mass fragmentography). The recovery from urine for the various compounds was between 80% and 100%. The detection limit for these compounds was in the range 0.01--0.05 micrograms/ml of urine. The method proved to be suitable for measuring urine concentrations for at least four days after administration of a single oral low therapeutic dose of the laxatives to sixteen healthy volunteers.