Chemotherapy dosing of the fluoropyrimidine 5-fluorouracil (5-FU) is currently based on body surface area. However, body surface area-based dosing has been associated with clinically significant pharmacokinetic variability, and as such, dosing based on body surface area may be of limited use. The clinical activity of 5-FU is modest at standard doses, and in general, dosing is limited by the safety profile, with myelosuppression and gastrointestinal toxicity being the most commonly observed side effects. Various strategies have been developed to enhance the clinical activity of 5-FU, such as biochemical modulation, alterations in scheduling of administration, and the use of oral chemotherapy. Studies that have shown an association between plasma concentration with toxicity and clinical efficacy have shown that pharmacokinetically guided dose adjustments can substantially improve the therapeutic index of 5-FU treatment. These studies have shown that only 20%-30% of patients treated with a 5-FU-based regimen have 5-FU levels that are in the appropriate therapeutic range--approximately 40%-60% of patients are underdosed and 10%-20% of patients are overdosed. To date, 5-FU drug testing has not been widely used because of the lack of a simple, fast, and inexpensive method. Recent advances in testing based on liquid chromatography-mass spectroscopy and a nanoparticle antibody-based immunoassay for 5-FU may now allow for routine monitoring of 5-FU in clinical practice. We review the data on pharmacokinetically guided dose adjustment of 5-FU and discuss the potential of this approach to advance therapeutic outcomes.

In recent years, there has been an increase in the number of reports in the U.S. of the use of drugs, often in conjunction with alcohol, to commit sexual assault. A study was undertaken to assess the prevalence of drug use in sexual assault cases in which substances are suspected of being involved. Law enforcement agencies, emergency rooms, and rape crisis centers across the U.S. were offered the opportunity to submit urine samples collected from victims of alleged sexual assault, where drug use was suspected, for analysis of alcohol and drugs which may be associated with sexual assault. Each sample was tested by immunoassay for amphetamines, barbiturates, benzodiazepines, cocaine metabolite (benzoylecgonine), cannabinoids, methaqualone, opiates, phencyclidine and propoxyphene. The positive screen results were confirmed by gas chromatography-mass spectroscopy (GC-MS). In addition, each sample was tested for flunitrazepam metabolites and gamma-hydroxybutyrate (GHB) by GC-MS and for ethanol by gas chromatography-flame ionization detection (GC-FID). Over a 26-month period, 1179 samples were collected and analyzed from 49 states, Puerto Rico, and the District of Columbia. The states sending the most samples were California (183), Texas (119), Florida (61), Pennsylvania (61), New York (61), Minnesota (50), Illinois (47), Indiana (44), Michigan (40), Maryland (37), Virginia (32), and Massachusetts (31). Four-hundred sixty eight of the samples were found negative for all the substances tested; 451 were positive for ethanol, 218 for cannabinoids, 97 for benzoylecgonine, 97 for benzodiazepines, 51 for amphetamines, 48 for GHB, 25 for opiates, 17 for propoxyphene, and 12 for barbiturates. There were no samples identified as positive for phencyclidine or methaqualone. In addition, 35% of the drug-positive samples contained multiple drugs. This study indicates that, with respect to alleged sexual assault cases, the prevalence of ethanol is very high, followed by cannabinoids, cocaine, benzodiazepines, amphetamines, and GHB. Although only a couple of substances have been implicated with sexual assault, this study has shown that almost 20 different substances have been associated with this crime. This study also raises the concern of illicit and licit drug use in sexual assault cases and suggests the need to test for a range of drugs in these cases. It also highlights the need to test for GHB, which is not generally tested for in a normal toxicology screen.

In Europe and the United States, the recreational use of gamma-hydroxy butyric acid (GHB) at dance clubs and "rave" parties has increased substantially. In addition, GHB is used to assist in the commission of sexual assaults. The aim of this controlled clinical study was to acquire pharmacokinetic profiles, detection times, and excretion rates in human subjects. Eight GHB-naïve volunteers were administered a single 25-mg/kg body weight oral dose of GHB, and plasma, urine, and oral fluid specimens were analyzed by using gas chromatography-mass spectrometry (GC-MS). Liquid-liquid extraction was performed after acid conversion of GHB to gamma-butyrolactone. Limits of quantitation of 0.1 (oral fluid), 0.2 (urine), and 0.5 microg/mL (plasma) could be achieved in the selected ion monitoring mode. GHB plasma peaks of 39.4 +/- 25.2 microg/mL (mean +/- SEM) occurred 20-45 min after administration. The terminal plasma elimination half-life was 30.4 +/- 2.45 min, the distribution volume 52.7 +/- 15.0 L, and the total clearance 1228 +/- 233 microL/min. In oral fluid, GHB could be detected up to 360 min, with peak concentrations of 203 +/- 92.4 microg/mL in the 10-min samples. In urine, 200 +/- 71.8 and 230 +/- 86.3 microg/mL, were the highest GHB levels measured at 30 and 60 min, respectively. Only 1.2 +/- 0.2% of the dose was excreted, resulting in a detection window of 720 min. Common side-effects were confusion, sleepiness, and dizziness; euphoria and change of vital functions were not observed. GHB is extensively metabolized and rapidly eliminated in urine and oral fluid. Consequently, samples should be collected as soon as possible after ingestion.

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Recognizing that international collaboration is critical for the acceleration of biomarker standardization efforts and the efficient development of improved diagnosis and therapy, the Alzheimer's Association created the Global Biomarkers Standardization Consortium (GBSC) in 2010. The consortium brings together representatives of academic centers, industry, and the regulatory community with the common goal of developing internationally accepted common reference standards and reference methods for the assessment of cerebrospinal fluid (CSF) amyloid β42 (Aβ42) and tau biomarkers. Such standards are essential to ensure that analytical measurements are reproducible and consistent across multiple laboratories and across multiple kit manufacturers. Analytical harmonization for CSF Aβ42 and tau will help reduce confusion in the AD community regarding the absolute values associated with the clinical interpretation of CSF biomarker results and enable worldwide comparison of CSF biomarker results across AD clinical studies.