A new approach to detecting sugar syrup addition to honey: Stable isotope analysis of hexamethylenetetramine synthesised from honey monosaccharides (fructose and glucose).

One of the most common types of adulteration of honey involves the addition of invert sugar syrups. A new method was developed to measure the stable isotope ratios of carbon and carbon-bound non-exchangeable (CBNE) hydrogen from specific molecular positions in fructose and glucose in honey. This was achieved through periodate oxidation of the sugars to produce formaldehyde, followed by reaction with ammonia to form hexamethylenetetramine (HMT).

Assessment of rapid low-cost isotope (δ N, δ O) analyses of nitrate in fruit extracts by Ti(III) reduction to differentiate organic from conventional production.

Rationale: The isotopic composition (δ N, δ O) of nitrate in fruits and vegetables differentiates organic from conventional food production practices. Organic systems do not use synthetic nitrate fertilizers high in O and low in N and thereby help reveal producers' fertilization claims. Isotope analyses of nitrate extracted from fruits and vegetables are done by bacterial reduction which is costly and by specialized laboratories.

Detection of exogenous sugars in pineapple juice using compound-specific stable hydrogen isotope analysis.

An improved procedure for determining H/H isotope ratios, using gas chromatography-isotope ratio mass spectrometry, has been used to detect the addition of exogenous C4-plant-derived sugars to pineapple juice. Isotopic techniques are commonly used to identify the addition of low-cost sugars to fruit juices and are difficult to subvert as it is not economically viable to change the isotopic ratios of the sugars. However, the addition of cane sugar to pineapple juice has presented a significant challenge that is only detected by site-specific C analysis of the methyl and methylene positions of ethanol derived from pineapple sugars, measured by nuclear magnetic resonance.

Food Matrix Reference Materials for Hydrogen, Carbon, Nitrogen, Oxygen, and Sulfur Stable Isotope-Ratio Measurements: Collagens, Flours, Honeys, and Vegetable Oils.

An international project developed, quality-tested, and measured isotope-delta values of 10 new food matrix reference materials (RMs) for hydrogen, carbon, nitrogen, oxygen, and sulfur stable isotope-ratio measurements to support food authenticity testing and food provenance verification. These new RMs, USGS82 to USGS91, will enable users to normalize measurements of samples to isotope-delta scales. The RMs include (i) two honeys from Canada and tropical Vietnam, (ii) two flours from C3 (rice) and C4 (millet) plants, (iii) four vegetable oils from C3 (olive, peanut) and C4 (corn) plants, and (iv) two collagen powders from marine fish and terrestrial mammal origins.

Stable isotope analysis of non-exchangeable hydrogen in carbohydrates derivatised with N-methyl-bis-trifluoroacetamide by gas chromatography - Chromium silver reduction/High temperature Conversion-isotope ratio mass spectrometry (GC-CrAg/HTC-IRMS).

A novel procedure for the rapid isotope analysis of the carbon-bound non-exchangeable (CBNE) hydrogen in mono and disaccharides has been developed to demonstrate the feasibility of detecting undeclared addition of exogenous sugar products in foods and beverages susceptible to economically motivated adulteration. The procedure utilizes a simple one-step reaction, with the derivatising agent N-methyl-bis-trifluoroacetamide, to substitute the exchangeable hydroxyl-hydrogens with trifluoroacetate derivatives that are sufficiently volatile to be separated and measured by a gas chromatograph coupled to an isotope ratio mass spectrometer. The conversion of the derivatised sugars into the measuring gas is achieved using a high temperature chromium-silver reactor that retains carbon, oxygen and fluorine whilst releasing hydrogen gas for stable isotope measurement.

A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil.

Background And Objective: In microdose studies, the pharmacokinetic profile of a drug in blood after administration of a dose up to 100 μg is measured with sensitive analytical techniques, such as accelerator mass spectrometry (AMS). As most drugs exert their effect in tissue rather than blood, methodology is needed for extending pharmacokinetic analysis to different tissue compartments. In the present study, we combined, for the first time, AMS analysis with positron emission tomography (PET) in order to determine the pharmacokinetic profile of the model drug verapamil in plasma and brain of humans.

Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET.

Purpose: The aim of this study was to assess the influence of age on the functional activity of the multidrug efflux transporter P-glycoprotein (P-gp) at the human blood-brain barrier.

Methods: Seven young (mean age: 27 +/- 4 years) and six elderly (mean age: 69 +/- 9 years) healthy volunteers underwent dynamic (R)-[(11)C]verapamil (VPM) positron emission tomography (PET) scans and arterial blood sampling. Parametric distribution volume (DV) images were generated using Logan linearisation, and age groups were compared with statistical parametric mapping (SPM).

Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET.

Unlabelled: The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB.

Peripheral metabolism of (R)-[11C]verapamil in epilepsy patients.

Purpose: (R)-[(11)C]verapamil is a new PET tracer for P-glycoprotein-mediated transport at the blood-brain barrier. For kinetic analysis of (R)-[(11)C]verapamil PET data the measurement of a metabolite-corrected arterial input function is required. The aim of this study was to assess peripheral (R)-[(11)C]verapamil metabolism in patients with temporal lobe epilepsy and compare these data with previously reported data from healthy volunteers.

Pharmacoresistance in epilepsy: a pilot PET study with the P-glycoprotein substrate R-[(11)C]verapamil.

Purpose And Methods: Regional overexpression of the multidrug transporter P-glycoprotein (P-gp) in epileptic brain tissue may lower target site concentrations of antiepileptic drugs and thus contribute to pharmacoresistance in epilepsy. We used the P-gp substrate R-[(11)C]verapamil and positron emission tomography (PET) to test for differences in P-gp activity between epileptogenic and nonepileptogenic brain regions of patients with drug-resistant unilateral temporal lobe epilepsy (n = 7). We compared R-[(11)C]verapamil kinetics in homologous brain volumes of interest (VOIs) located ipsilateral and contralateral to the seizure focus.

A pilot study testing whether concentrations of levofloxacin in interstitial space fluid of soft tissues may serve as a surrogate for predicting its pharmacokinetics in lung.

Recent observations indicate that pharmacokinetics of beta-lactam antibiotics in the lung can be predicted by the use of concentration versus time profiles in peripheral soft tissues. If this observation is transferred to other classes of antimicrobials, measurement of antimicrobial concentrations in peripheral tissues would enable prediction of the pharmacokinetics of antimicrobials at the site of the respiratory tract infection. We set out to test the hypothesis that concentrations of the fluoroquinolone levofloxacin in the respiratory tract can be predicted on the basis of knowledge of its pharmacokinetics in peripheral soft tissues.

A positron emission tomography microdosing study with a potential antiamyloid drug in healthy volunteers and patients with Alzheimer's disease.

This work describes a microdosing study with an investigational, carbon 11-labeled antiamyloid drug, 1,1'-methylene-di-(2-naphthol) (ST1859), and positron emission tomography (PET) in healthy volunteers (n = 3) and patients with Alzheimer's disease (n = 6). The study aimed to assess the distribution and local tissue pharmacokinetics of the study drug in its target organ, the human brain. Before PET studies were performed in humans, the toxicologic characteristics of ST1859 were investigated by an extended single-dose toxicity study according to guidelines of the Food and Drug Administration and European Medicines Agency, which are relevant for clinical trials with a single microdose.

Combined PET and microdialysis for in vivo assessment of intracellular drug pharmacokinetics in humans.

Unlabelled: Because many drugs possess an intracellular site of action, the knowledge of intracellular concentration-time profiles is desirable. In the present study, PET, which measures total (i.e.