J Wijsbeek

A Single-Column Procedure on Bond Elut Certify for Systematic Toxicological Analysis of Drugs in Plasma and Urine

A single-column solid-phase extraction procedure was developed for the screening of acidic, neutral, and basic drugs from plasma. The recoveries of all 25 tested drugs exceeded 82%. After the plasma had been diluted with phosphate buffer (pH 6.0), the drugs were extracted using a single Bond Elut Certify column. The acidic and most of the neutral drugs were eluted by acetone/chloroform (1:1) and the basic drugs were eluted by 2% ammoniated ethyl acetate. Some neutral drugs appeared in both fractions. The two fractions were collected separately and evaporated until approximately 100 microL of solvent remained in the tube. Both fractions were analyzed separately on a gas chromatograph equipped with a wide-bore capillary column and a flame ionization detector. The procedure could also be used for urine samples.

Cannabinoids with a propyl side chain in cannabis: occurrence and chromatographic behavior

Neutral cannabinoids with a pentyl side chain—for example, cannabidiol, tetrahydrocannabinol, and cannabinol—are generally accompanied by homologs with a propyl side chain, of which at least one has psychotropic activity. Samples of hashish and marihuana from Asia especially sometimes have abundant amounts of propyl cannabinoids, the quantities being of the same order as that of the accompanying pentyl cannabinoids. Detection and identification of the propyl and pentyl cannabinoids in gas chromatography and thin-layer chromatography is discussed.

INTERLABORATORY APPLICABILITY OF A RETENTION INDEX LIBRARY OF DRUGS FOR SCREENING BY REVERSED-PHASE HPLC IN SYSTEMATIC TOXICOLOGICAL ANALYSIS

Abstract The retention indices (RI) of 47 selected acidic, neutral and basic drugs were determined on 7 reversed-phase (octyl- and octadecylsilica) columns in two laboratories in the 1-nitroalkane scale, using either 1-nitroalkane homologues or selected drugs, whose RI values were previously determined on the reference column. Obtained values were compared with the library values, determined previously on the reference column. Retention indices, calculated with drugs as RI markers, showed distinctly lower deviations from the library values and lower inter-column variability: The mean standard deviation of RI for all drugs analyzed on all columns in the 1-nitroalkane scale was 44.3 RI units, against 10.3 units when selected drugs were used as RI markers. The deviations from the listed values, calculated for each column separately with drugs as markers, were in 95% of cases smaller than 20 RI units, and in 80 % smaller than 10 units. The largest differences between the experimental and listed values were ob...

Interference of alkanes in the gas chromatographic analysis of cannabis products

Leaves of young marihuana plants (Cannabis sativa L.) were found by gas liquid chromatography to contain appreciable amounts of two long‐chain alkanes, n‐heptacosane and n‐nonacosane. These alkanes, along with other straight chain alkanes ranging from C19 to C32 could also be detected as minor components in a variety of other marihuana and hashish samples. Depending on the polarity of the g.l.c. column used, the alkanes may have retention times similar to those of the major cannabinoids and thus interfere with qualitative and quantitative analyses of the latter. The findings indicate that g.l.c. alone cannot be used as an accurate and reliable technique for cannabinoid analysis, unless the alkanes are previously removed. However, the alkane composition may be of additional advantage in determining the origin of seized cannabis samples.

DETERMINATION OF LOW CONCENTRATIONS OF QUATERNARY AMMONIUM COMPOUND THIAZINAMIUM METHYLSULFATE IN PLASMA AND URINE

A sensitive and selective method for the quantitative determination of the quaternary ammonium antiacetylcholine‐compound thiazinamium methylsulphate (Multergan) in plasma and urine is described. The procedure is based on ion pair extraction of the compound with iodide as the counter ion. This is followed by gas chromatography using an alkali flame ionization detector. The detection limit is 2 ng ml−1 with a recovery of 88·0 ± 6·2% from plasma, 91·4 ± 4·6% from urine. The described method can also be applied to other quaternary ammonium compounds.

Semi-automated solid-phase extraction procedure for drug screening in biological fluids using the ASPEC system in combination with Clean Screen DAU columns

The use of a semi-automated solid-phase extraction system (ASPEC) for the screening of drugs in plasma and urine on a single mixed-mode column (Clean Screen DAU) is described. The processes of column preconditioning, sample application, column wash, pH adjustment and elution of the drugs were accomplished by the ASPEC. After off-line evaporation, the residues were injected into a wide-bore capillary gas chromatograph. The recoveries of the tested drugs were in the range of 73-96%, with relative standard deviations less than 5% at a concentration level of 2 micrograms/ml.

STUDY OF LOT-TO-LOT REPRODUCIBILITIES OF BOND ELUT CERTIFY AND CLEAN SCREEN DAU MIXED-MODE SOLID-PHASE EXTRACTION COLUMNS IN THE EXTRACTION OF DRUGS FROM WHOLE-BLOOD

The lot-to-lot reproducibilities of Bond Elut Certify and Clean Screen DAU columns are described. The recoveries of five test drugs obtained from twelve lots of Bond Elut Certify columns ranged from 84 to 104% with standard deviations of less than 9%. The recoveries of five test drugs obtained from six lots of Clean Screen DAU columns ranged from 81 to 103% with standard deviations of less than 7%. The 95% confidence intervals of the means as obtained by ANOVA demonstrate that there are no significant differences between the tested lots of Bond Elut Certify and Clean Screen DAU columns. Comparison of the two brands shows that both Bond Elut Certify and Clean Screen DAU columns are well acceptable for routine drug screening in systematic toxicological analysis, with a slightly higher overall recovery for the former.

Interlaboratory Reproducibility of Retention Indices in Capillary Gas Chromatography

Because of the temperature-dependent behavior of Kovats retention indices (RI), based on straight-chain alkane homologues and a liquid phase such as SE-30. OV-1. or methyl silicone, the interlaboratory reproducibility of these RIs determined on capillary columns is comparable to those determined on packed columns. Other homologue series investigated—including diisopropyl-n-alkylamines (DIPA), tri-n-alkylamines (TAA), and 1-nitro-n-alkanes (NIA)—showed the same phenomenon. However, by using a carefully selected reference drug mixture, a dramatic gain in the interlaboratory reproducibility of RI values can be obtained, even under vastly different operational conditions. This allows a search window of ±25 RI units for capillary methyl silicone columns, which is much better than the ±60 RI units that must be applied when using alkane or substituted alkane homologues.

Variations in the bioavailability of thiazinamium methylsulfate

Bioavailability after oral administration of the anticholinergic drug thiazinamium methylsulfate (Multergan), a phenothiazine derivative with a quaternary ammonium group in the moleeule, has been studied in patients and volunteers by measuring the drug concentrations in plasma or the excretion of the parent drug in urine. The relative bioavailability as compared to intramuscular injection seems to be of the order of 10%. Much more of the drug is absorbed, however, but is metabolized during the first liver passage. Moreover, there seems to be a substantial interindividual variation in the bioavailability of the drug. Studies in a group of eight volunteers showed that there is also a substantial intraindividual variation, but its magnitude is smalter than that of the interindividual variation.

DETERMINATION OF CARBISOCAINE, HEPTACAINE AND PENTACAINE IN PLASMA BY CAPILLARY GAS-CHROMATOGRAPHY WITH NITROGEN-SELECTIVE DETECTION

A gas-liquid chromatographic method is described for the determination of the local anaesthetics carbisocaine, heptacaine and pentacaine in plasma. A C(18) solid-phase extraction was used in a modification to increase selectivity. Following on-column derivatization with trimethylanilinium hydroxide, the analytes were determined by means of capillary gas chromatography and nitrogen-phosphorus selective detection. In comparison with flame ionization detection, the sensitivity of NPD was 20 times higher with a limit of determination in plasma of 10 ng ml(-1).