Water sorption and near IR spectroscopy to study the differences between microcrystalline cellulose and silicified microcrystalline cellulose before and after wet granulation.

Silicified microcrystalline cellulose (SMCC) has been shown to have advantages over conventional microcrystalline cellulose (MCC). These advantages are (i) improved tablet strength compared to that achieved with MCC, (ii) the retention of compressibility after wet granulation, whereas MCC produces weaker tablets after wet granulation, and (iii) superior flow properties than MCC. In this study gravimetric and calorimetric vapour sorption data and near IR spectroscopy have been used to study MCC and SMCC before and after wet granulation. It was found that MCC, SMCC and wet granulated SMCC had essentially identical physical structures (except for a size increase due to granulation). Wet granulated MCC had a different enthalpy of water sorption at low RH, and its near IR spectrum was different from the other samples in the region which relates to C-H bonding. It can be concluded that MCC and SMCC are of very similar structures, thus these analytical techniques cannot provide an explanation for the improvements in compressibility. However the change in compressibility in MCC after wet granulation may relate to the observed differences in internal bonding in this sample.

Identification in human urine of delta 9-tetrahydrocannabinol-11-oic acid glucuronide: a tetrahydrocannabinol metabolite.

A delta 9-THC metabolite has been identified in human urine as an ester linked glucuronide of delta 9-THC-11-oic acid. Its identity was established by a comparison of mass spectra from the metabolite extracted from human urine and synthetically prepared material. delta 9-THC-11-oic acid glucuronide was found to be responsible for the major part of RIA cross-reactivity in urine with the Guildhay cannabinoid antiserum used in this study.

Rapid identification of Digitalis purpurea using near-infrared reflectance spectroscopy.

Glycosides from Digitalis are widely used for the treatment of various cardiac conditions. The potential for near-infrared (NIR) spectroscopy as a technique for the rapid identification of Digitalis purpurea was studied. If successful, this method would be advantageous over traditional methods which are destructive and time-consuming. It was possible to identify D. purpurea from other plants using a Maximum Distance in Wavelength Space statistical comparison method on standard normal variate-corrected, second-derivative spectra. Match values ranged from 1.65 to 2.26 for correct identification and were greater than 11.2 [corrected] for other plants. It was also possible to discriminate between different plant parts of D. purpurea, with match values ranging from 1.52 to 2-26 for leaves and greater than 29 for other parts of the same plant. The use of correlation coefficients and the Correlation in Wavelength Space methods proved less conclusive, with resulting values for leaves from different plants being very high, and in all but one case, above 0.9. A two-wavelength, nearest neighbours analysis was carried out for de-trended (baseline corrected), standard normal variate-corrected spectra at 1150 and 2160 nm. This resulted in the successful identification of unknown samples. NIR spectroscopy has the potential for the rapid identification of D. purpurea, and possibly for other natural products of pharmaceutical interest.

A near-infrared method for the assay of cineole in eucalyptus oil as an alternative to the official BP method.

Thirty different eucalyptus oil samples were scanned on the FOSS NIRSystems 6500 Rapid Content Sampler using a reflectance vessel as sample presentation method. The cineole content of each sample was determined by the BP method and these reference data were used to construct two calibration equations for cineole content in the oils using Vision software. The mean accuracy for the NIR method differed by 1.01% or less, and the mean bias by +/-0.33% or less, compared with the BP method. Calculation of the 95% confidence intervals for the slope and intercept of plots of NIR predicted values against BP method reference values showed that there was no evidence of fixed or relative systematic errors. Tests for short-term and intermediate repeatability were conducted. The standard deviation was 0.83% w/w or less and the coefficient of variation was 1.11% or less. The confidence intervals for both short-term and intermediate repeatability overlapped with that for the BP method, suggesting that there was no evidence for a difference in values obtained by the BP and NIR methods. The range of cineole contents used in the calibrations was extended by incorporating five samples of eucalyptus oil spiked with cineole, and five samples of two essential oils known to have a lower cineole content than eucalyptus oil, to give a range of 52.5 to 99.0% w/w. The mean accuracy decreased to an error of 1.26% or less and the bias to +/-0.50% or less. Again, confidence intervals suggested there was no evidence for fixed or systematic errors in the NIR calibrations. We propose that NIR spectroscopy could be used as an alternative method for the determination of cineole content in eucalyptus oils.

Passive inhalation of cannabis smoke.

Six volunteers each smoked simultaneously, in a small unventilated room (volume 27 950 litre), a cannabis cigarette containing 17.1 mg delta 9-tetrahydrocannabinol (THC). A further four subjects - passive inhalers - remained in the room during smoking and afterwards for a total of 3 h. Blood and urine samples were taken from all ten subjects and analysed by radioimmunoassay for THC metabolites. The blood samples from the passive subjects taken up to 3 h after the start of exposure to cannabis smoke showed a complete absence of cannabinoids. In contrast, their urine samples taken up to 6 h after exposure showed significant concentrations of cannabinoid metabolites (less than or equal to 6.8 ng ml-1). These data, taken with the results of other workers, show passive inhalation of cannabis smoke to be possible. These results have important implications for forensic toxicologists who are frequently called upon to interpret cannabinoid levels in body fluids.

Forensic aspects of the metabolism and excretion of cannabinoids following oral ingestion of cannabis resin.

Following oral ingestion of cannabis resin, delta 9-THC-11-oic acid and its O-ester glucuronide were detected using RIA and combined hplc/RIA and shown to be major plasma metabolites of delta 9-THC. delta 9-THC-11-oic acid was not excreted in the urine in significant concentrations, the glucuronide conjugate being the major urinary metabolite detected. delta 9-THC metabolites were detected in blood for up to 5 days and in urine for up to 12 days following a single oral dose of delta 9-THC (20 mg). Estimates for the half life of delta 9-THC-11-oic acid and its glucuronide in plasma, and total metabolites in urine have been obtained. Interpretation of blood or urine total cannabinoid levels is most difficult, however, drug/metabolite ratios and metabolite/metabolite ratios may have potential for indicating recent cannabis use.

The development and evaluation of a 125I radioimmunoassay for the measurement of LSD in body fluids.

A radioimmunoassay (RIA) has been developed for the direct detection of LSD in biological fluids. The radiotracer, (+)-2-[125I]iodo-LSD, allows the use of gamma-counting rather than the liquid scintillation counting currently used for existing 3H radioimmunoassays. The assay is specific for LSD and very closely related compounds. It is inexpensive, sensitive, simple to use and small volumes of samples (50 microliter) can be assayed directly without the need for any time-consuming extraction procedures. The cut-off levels are 1.2 ng/ml in blood and 3.0 ng/ml in urine. The results obtained using the 125I assay described in this work compare very favourably with those obtained using the 3H assay currently used by Home Office Forensic Science Laboratories. The advantages of the assay make it a most appropriate method for the routine screening of LSD in biological samples of forensic interest.

Confirmation of cannabis use by the analysis of delta 9-tetrahydrocannabinol metabolites in blood and urine by combined HPLC and RIA.

Cannabis use is confirmed through the analysis of blood and urine using combined high-performance liquid chromatography/radioimmunoassay to detect delta 9-THC-11-oic acid and its O-ester glucuronide (the major delta 9-THC metabolites). The method is sensitive and specific and will allow the complete analysis of at least six samples per day. It has been successfully applied to the analysis of samples submitted for forensic analysis and, in combination with a previously described radioimmunoassay, offers a useful approach to routine toxicological analysis of cannabinoid metabolites.

A novel 125I radioimmunoassay for the analysis of delta 9-tetrahydrocannabinol and its metabolites in human body fluids.

A cannabinoid radioimmunoassay (RIA) that detects some of the major delta 9-THC metabolites is developed and evaluated for use in forensic science. It incorporates a novel 125I radiotracer, is sensitive, reliable, relatively quick, and simple to use. The RIA uses a commercially available antiserum and detects a number of cannabinoid metabolites, including delta 9-THC-11-oic acid and its glucuronide conjugate in biological fluids. The method was successfully applied to the analysis of blood and urine samples submitted for forensic analysis.

A collaborative study to investigate the retention reproducibility of barbiturates in HPLC with a view to establishing retention databases for drug identification.

A collaborative study among 10 laboratories has been undertaken to investigate the interlaboratory reproducibility of retention measurements in a high performance liquid chromatographic (HPLC) system for separating barbiturates. The system involved an ODS-Hypersil column with an eluent of methanol:phosphate buffer (40:60, v/v) at pH 8.5; all laboratories used the same batch of packing material. The conventional methods of recording retention properties (retention times and capacity factors) gave poor interlaboratory reproducibility. Better results were obtained by expressing the retentions relative to a standard barbiturate (quinalbarbitone); relative adjusted retention times proved to be more effective than straightforward relative retention times. Retention indices based on the alkylarylketone scale were not as reproducible as the methods based on a single closely related compound. The best reproducibility was obtained using corrected capacity factors based on the retention of four barbiturates in a standard mixture. The results of the study are discussed with a view to selecting the best methods of recording retention in HPLC when considering the establishment of databases for drug identification.

Changes in pulmonary function tests during spinal anaesthesia for caesarean section.

We report the changes in forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow rate during caesarean section under spinal anaesthesia, as indirect indices of the ability to cough effectively. There were progressive falls in forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) from the onset of anaesthesia till the abdomen was open, with these results failing to return to pre-incision levels by the time the patient reached the recovery room. Although none of our patients complained of dyspnoea or difficulty in coughing such falls in PEFR and FEV(1) may lead to an inability to cough effectively or clear inhaled vomit especially in patients with previously impaired respiratory function.