Data on the detection times of drugs of abuse are based on studies of controlled administration to volunteers or on the analysis of biologic samples of subjects who are forced to stop their (often chronic) use of drugs of abuse, eg, because of imprisonment or detoxification. The detection times depend mainly on the dose and sensitivity of the method used and also on the preparation and route of administration, the duration of use (acute or chronic), the matrix that is analyzed, the molecule or metabolite that is looked for, the pH and concentration of the matrix (urine, oral fluid), and the interindividual variation in metabolic and renal clearance. In general, the detection time is longest in hair, followed by urine, sweat, oral fluid, and blood. In blood or plasma, most drugs of abuse can be detected at the low nanogram per milliliter level for 1 or 2 days. In urine the detection time of a single dose is 1.5 to 4 days. In chronic users, drugs of abuse can be detected in urine for approximately 1 week after last use, and in extreme cases even longer in cocaine and cannabis users. In oral fluid, drugs of abuse can be detected for 5-48 hours at a low nanogram per milliliter level. The duration of detection of GHB is much shorter. After a single dose of 1 or 2 ng of flunitrazepam, the most sensitive methods can detect 7-aminoflunitrazepam for up to 4 weeks in urine.

GC is commonly used for the analysis of cannabis samples, e.g. in forensic chemistry. However, as this method is based on heating of the sample, acidic forms of cannabinoids are decarboxylated into their neutral counterparts. Conversely, HPLC permits the determination of the original composition of plant cannabinoids by direct analysis. Several HPLC methods have been described in the literature, but most of them failed to separate efficiently all the cannabinoids or were not validated according to general guidelines. By use of an innovative methodology for modelling chromatographic responses, a simple and accurate HPLC/DAD method was developed for the quantification of major neutral and acidic cannabinoids present in cannabis plant material: Delta9-tetrahydrocannabinol (THC), THC acid (THCA), cannabidiol (CBD), CBD acid (CBDA), cannabigerol (CBG), CBG acid (CBGA) and cannabinol (CBN). Delta8-Tetrahydrocannabinol (Delta8-THC) was determined qualitatively. Following the practice of design of experiments, predictive multilinear models were developed and used in order to find optimal chromatographic analytical conditions. The method was validated following an approach using accuracy profiles based on beta-expectation tolerance intervals for the total error measurement, and assessing the measurements uncertainty. This analytical method can be used for diverse applications, e.g. plant phenotype determination, evaluation of psychoactive potency and control of material quality.

Among critically ill patients with normal kidney function, a strategy of dose adaptation based on daily TDM led to an increase in PK/PD target attainment compared to conventional dosing.

BackgroundCorrect antibiotic dosing remains a challenge for the clinician. The aim of this study was to assess the influence of augmented renal clearance on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving meropenem or piperacillin/tazobactam, administered as an extended infusion.MethodsThis was a prospective, observational, pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center. Elegible patients were adult patients without renal dysfunction receiving meropenem or piperacillin/tazobactam as an extended infusion. Serial blood samples were collected to describe the antibiotic pharmacokinetics. Urine samples were taken from a 24-hour collection to measure creatinine clearance. Relevant data were drawn from the electronic patient file and the intensive care information system.ResultsWe obtained data from 61 patients and observed extensive pharmacokinetic variability. Forty-eight percent of the patients did not achieve the desired pharmacokinetic/pharmacodynamic target (100% fT>MIC), of which almost 80% had a measured creatinine clearance >130 mL/min. Multivariate logistic regression demonstrated that high creatinine clearance was an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target. Seven out of nineteen patients (37%) displaying a creatinine clearance >130 mL/min did not achieve the minimum pharmacokinetic/pharmacodynamic target of 50% fT>MIC.ConclusionsIn this large patient cohort, we observed significant variability in pharmacokinetic/pharmacodynamic target attainment in critically ill patients. A large proportion of the patients without renal dysfunction, most of whom displayed a creatinine clearance >130 mL/min, did not achieve the desired pharmacokinetic/pharmacodynamic target, even with the use of alternative administration methods. Consequently, these patients may be at risk for treatment failure without dose up-titration.

Aim A major problem in assessing the true public health impact of drug-use on driving and overall traffic safety is that the variables being measured across studies vary significantly. In studies reported in a growing global literature, basic parameters assessed, analytical techniques and drugs tested are simply not comparable due to lack of standardization in the field. These shortcomings severely limit the value of this research to add knowledge to the field. A set of standards to harmonize research findings is sorely needed. This project was initiated by several international organizations to develop guidelines for research on drugged driving. Methods A September 2006 meeting of international experts discussed the harmonization of protocols for future research on drugged driving. The principal objective of the meeting was to develop a consensus report setting guidelines, standards, core data variables and other controls that would form the basis for future international research. A modified Delphi method was utilized to develop draft guidelines. Subsequently, these draft guidelines were posted on the internet for global review, and comments received were integrated into the final document. Results The Guidelines Document is divided into three major sections, each focusing upon different aspects of drugged driving research (e.g. roadside surveys, prevalence studies, hospital studies, fatality and crash investigations, etc.) within the critical issue areas of ‘behavior’, ‘epidemiology’ and ‘toxicology’. The behavioral section contains 32 specific recommendations; (2) epidemiology 40 recommendations; and (3) toxicology 64 recommendations. Conclusions It is anticipated that these guidelines will improve significantly the overall quality of drugged driving research and facilitate future cross-study comparisons nationally and globally.