P. Daenens

Determination of Cotinine in Biological-fluids By Capillary Gas-chromatography Mass-spectrometry - Selected-ion Monitoring

A sensitive and selective method for the determination of cotinine in plasma and urine is presented. Quantitation is effected by capillary gas chromatography-mass spectrometry after liquid--liquid extraction of 0.25-1 ml of biological specimens with a trideuterated cotinine internal standard. The procedure is linear and has acceptable precision over the range of concentrations encountered in pharmacokinetic studies of nicotine or cotinine. The suitability of the assay is shown by a number of plasma concentration--time curves after a single oral or intravenous administration of cotinine to a human volunteer and after multiple-dose intravenous administration of nicotine.

Analysis of buprenorphine in urine specimens

The simultaneous determination of buprenorphine (Temgesic) and its major metabolite, N-desalkylbuprenorphine, in urine samples has been studied. By using reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection, therapeutic concentrations of unconjugated buprenorphine down to 0.2 ng/mL, and 0.15 ng/mL for the metabolite, can be detected in urine samples. This method has been applied to a variety of urine samples from drug users. The possible analytical interference from several other regulated drugs has been studied. The results were also compared with those obtained from a commercial radioimmunoassay (RIA) test. This test is only capable of detecting buprenorphine concentrations higher than 1 ng/mL.

Development of a radioimmunoassay for the determination of buprenorphine in biological samples

The development of a specific and sensitive radioimmunoassay for the detection of buprenorphine in urine samples is described. With minor adjustments, the assay was also applied to the analysis for buprenorphine in plasma samples. The 2-diazobenzoic acid derivative of buprenorphine has been prepared as a hapten. The immunization of rabbits with the hapten-bovine serum albumin conjugate resulted in the production of antibodies, which cross-reacted with N-dealkylbuprenorphine up to about the 90% level. The antibodies showed very low cross-reactivities with the 3-O-glucuronides and with the structural analogue etorphine. The assay was mainly used to pre-screen for buprenorphine in urine samples of persons suspected of Temgesic misuse and to determine buprenorphine in plasma samples. A linear calibration graph for buprenorphine was obtained after logit-log regression [Y = 0.383 (s, 0.059) - 0.535 X (s, 0.025); r = 0.997 (s, 0.001)]. The spiking recovery study showed a linear regression of Y (observed) = 0.94 + 0.84 X (expected); r = 0.997. Intra- and inter-assay relative standard deviations were < 4.35 and < 6.36%, respectively. A comparison study of the high-performance liquid chromatographic determination (X) to the radioimmunoassay (Y) resulted in the following regression equation for the urine samples: Y = 1.44 + 1.64 X (n = 32; r = 0.910) and Y = 0.007 + 1.58 X (n = 10; r = 0.930) for plasma specimens. The minimum detectable dose of the immunoassay was calculated to be 10 pg ml-1 (Students t-distribution, p = 0.01, degrees of freedom = 8).

The Identification of Quinazolinones on the Illicit Market

The abuse of hypnotics of the quinazolinone series is well known. Methaqualone [2-methyl-3-o-tolyl-4 (3H)-quinazolinone] in both licit and illicit tablets is encountered with increasing frequency. Several papers have discussed the identification of this drug in tablets and biological materials. Its metabolism has been studied in man [1–4] and animals [5,6]. Concentrations in urine, blood, and organs in cases of poisoning have been established [7–11].

A death case involving tilidine.

A fatal poisoning case due to the combination of a relative overdose of barbiturates (600 mg daily) and 750 mg of tilidine is reported. The concentrations of barbiturates and tilidine with its metabolites were determined in blood, liver, and urine.ZusammenfassungEine tödliche Vergiftung durch die Kombination mit einer relativen Überdosis von Barbituraten (täglich 600 mg) mit 750 mg Tilidin wird beschrieben. Die Barbituratspiegel in Blut, Leber und Urin sowie die Konzentrationen von Tilidin und zwei Stoffwechselprodukten wurden bestimmt.

Mass spectrometry-gas chromatographic determination of mecloqualone metabolites from urine extracts

SummaryThe separation and identification of metabolites of mecloqualone in human urine samples by GLC-MS analysis are described. Four hydroxylated mecloqualone derivates have been identified.ZusammenfassungDie Trennung und Identifizierung von Metaboliten des Mecloqualons in Menschenharn durch Gas-Flüssigchromatographie und Massenspektrometrie wurde beschrieben. Vier Hydroxylderivate des Mecloqualons wurden identifiziert.

Determination at the Nanogram Range of Rilatinic Acid in Urine After Ion-Pair Extraction

Ion-pair extraction and extractive alkylation of urine allows a simple, rapid, and very sensitive detection by TLC as well as EC-GLC tecnhiques, of rilatinic acid in small urine samples after the oral intake of therapeutic doses of methylphenidate.

Short comments to the paper of J. Klapetek

Results of toxicological analysis on the stomacal content were indeed not mentioned in our paper. However, barbiturates were not detected, and only traces of tilidine were observed. Obviously the medicines were nearly completely absorbed. There is furthermore a controversion between several authors whether or not respiratory depression may occur with tilidine, as wel as this controversion is known for its dependence-producing potential 1. Most of the published papers referred to by the author relate to animal experiments or to experiments on humans folowing administration of therapeutic doses which can hardly be compared with the 750 mg dose ingested at once by the victim. Such situation is much more alike to the experiments of Romagnoli and Keats (obtained on humans and at high doses) who showed that tilidine at equianalgetic doses (10 mg of morphine is to be compared with 80 -100 mg of tilidine) is at least as potent as morphine in depressing respiration 2 (tildine was given by intravenous route but is also very readily absorbed from the commercial capsules). Nevertheless it was clearly pointed out as well in the abstracts as in the discussion of our paper that the death is due to the combined action of barbiturates and tlidine. The small dose of hydroxyzine ingested by the victim may have contributed as well.