Assessing Adherence to Antihypertensive Medication by Means of Dose-Dependent Reference Plasma Concentration Ranges and Ultra-High Performance Liquid Chromatography-Ion Trap Mass Spectrometry Analysis

Poor adherence to antihypertensive drug therapy is a well-recognized problem and can be assessed by mass spectrometry-based analyses of body fluids. However, contrary statements exist whether drug quantification in blood or qualitative screening in urine is more suitable. The present pilot study aimed to further elucidate the power of blood plasma drug concentrations for adherence monitoring by developing and validating a quantification procedure for nine antihypertensive drugs (amlodipine, bisoprolol, candesartan, canrenone, carvedilol, metoprolol, olmesartan, torasemide, and valsartan) in blood plasma using liquid–liquid extraction and an ultra-high-performance liquid chromatography-ion trap mass spectrometry analysis. The procedure should then be used for an adherence assessment and compared with the results of an established qualitative urine screening. Selectivity, carryover, matrix effect, accuracy, precision, dilution integrity, and stability were successfully validated, except for amlodipine. The applicability was demonstrated by analyzing 19 plasma samples containing 28 antihypertensive drugs and comparing the measured concentrations with calculated dose-dependent reference plasma concentration ranges. The interpretation of plasma concentrations was found to be more sophisticated and time-consuming than that of urine screening results, and adherence could not be assessed in two cases (10%) due to measured plasma concentrations below the lower limit of quantification. However, 14 out of 19 subjects were classified as adherent (75%) and three as nonadherent (15%), in contrast to 19 (100%) that were claimed to be adherent based on the results of the qualitative urine screening. Nevertheless, further data is needed to estimate whether plasma quantification is superior in terms of assessing adherence to antihypertensive medication.     

Surfactant presence in a multilayer polyelectrolyte–enzyme system improves its catalytic response

Self-assembling of poly(allylamine) containing an osmium polypyridil complex (PAOs) alternatively with sodium dodecyl sulfate (SDS) and glucose oxidase (GOx) generates a ternary multilayer system, (PAOs/SDS/PAOs/GOx)_n. The introduction of this anionic surfactant allows a sensitive increase of the polyelectrolyte and the enzyme uptake at pH 7.0, enhancing its catalytic behavior in presence of glucose more than 5 times, compared to the system (PAOs/GOx)_n constructed at the same pH. The balance between ionic and hydrophobic interactions in the construction of this system is discussed.     

Cooperative hydration of pyruvic acid in ice

About 3.5 +/- 0.3 water molecules are still involved in the exothermic hydration of 2-oxopropanoic acid (PA) into its monohydrate (2,2-dihydroxypropanoic acid, PAH) in ice at 230 K. This is borne out by thermodynamic analysis of the fact that QH(T) = [PAH]/[PA] becomes temperature independent below approximately 250 K (in chemically and thermally equilibrated frozen 0.1 < or = [PA]/M < or = 4.6 solutions in D2O), which requires that the enthalpy of PA hydration (DeltaHH approximately -22 kJ mol(-1)) be balanced by a multiple of the enthalpy of ice melting (DeltaHM = 6.3 kJ mol(-1)). Considering that: (1) thermograms of frozen PA solutions display a single endotherm, at the onset of ice melting, (2) the sum of the integral intensities of the 1deltaPAH and 1deltaPA methyl proton NMR resonances is nearly constant while, (3) line widths increase exponentially with decreasing temperature before diverging below approximately 230 K, we infer that PA in ice remains cooperatively hydrated within interstitial microfluids until they vitrify.     

Correlation effect in variable range hopping in n-InSb

The longitudinal resistance of n-InSb has been measured down to 30 mK in magnetic fields up to 40 kG. Variable range hopping was observed below 0.3 K in the non-metallic region induced by the magnetic field. The experimental results suggest that correlated multi-electron hopping makes important contributions to conductivity in the variable range hopping conduction in n-InSb. It is seen in the behaviour of both exponential and pre-exponential terms with respect to the magnetic field.     

Comparison of salivary sodium and potassium concentrations measured by handheld ion-selective electrode meters and an automated biochemical analyser

Ion-selective electrode pocket meters available for use with saliva could be a convenient tool to assess how diseases, drugs, exercise or nutrition affect salivary composition. This study compared salivary sodium and potassium concentrations measured by handheld LAQUAtwin meters and a fully-automated biochemical analyzer. Agreement between two methods was assessed with Passing-Bablok regression and Bland-Altman plots. LAQUAtwin meters measured lower values of both analytes and provided repeatable though not accurate results. The meters may serve as an alternative to laboratory methods to gain insight into between-group differences in electrolyte concentrations, or a concentration change induced by an experimental procedure.     

Light-induced structural changes in chiral liquid crystals

Novel light-sensitive chiral dopants are studied as a light-sensitive component in chiral liquid crystals which may be used in tunable optical devices. Light-induced cis-trans- isomerization of chiral dopants results in changes of helical twisting power which translates into variations of helical pitch. Due to the light absorption in the liquid crystal cell the pitch variation is non-uniform across the cell, which leads, at first, to a deformation of cholesteric layers, and then to the formation of cholesteric bubbles. The sequence of structural changes has a distinct visual pattern and occurs at the surface close to the UV light source. Small deformations of cholesteric layers and bubbles are unstable and disappear after removing UV irradiation. The increasing size of the cholesteric bubbles results in better stability; large bubbles do not disappear after removing UV light. A theoretical model is suggested to describe the undulations of cholesteric layers.     

A Bis(dipyridophenazine)(2‐(2‐pyridyl)pyrimidine‐4‐carboxylic acid)ruthenium(II) Complex with Anticancer Action upon Photodeprotection

Improving the selectivity of anticancer drugs towards cancer cells is one of the main goals of drug optimization; the prodrug strategy has been one of the most promising. A light‐triggered prodrug strategy is presented as an efficient approach for controlling cytotoxicity of the substitutionally inert cytotoxic complex [Ru(dppz)₂(CppH)](PF₆)₂ ( C1 ; CppH=2‐(2‐pyridyl)pyrimidine‐4‐carboxylic acid; dppz=dipyrido[3,2‐a:2′,3′‐c]phenazine). Attachment of a photolabile 3‐(4,5‐dimethoxy‐2‐nitrophenyl)‐2‐butyl (DMNPB) ester (“photocaging”) makes the otherwise active complex C1 innocuous to both cancerous (HeLa and U2OS) and non‐cancerous (MRC‐5) cells. The cytotoxic action can be successfully unleashed in living cells upon light illumination (350 nm), reaching similar level of activity as the parent cytotoxic compound C1 . This is the first substitutionally inert cytotoxic metal complex to be used as a light‐triggered prodrug candidate.     

Automated resolution of overlapping peaks in chromatographic data

Parallel factor analysis 2 (PARAFAC2) has been shown to be a powerful tool for resolution of complex overlapping peaks in chromatographic analyses. It is particularly useful because of its ability to handle shifts in the elution time mode and peak shape changes. Like all curve resolution techniques, PARAFAC2 will only find chemically meaningful parameters (elution time profiles and mass spectra) if the correct number of factors are determined. So far, the primary way to determine an appropriate number of factors, when using PARAFAC2, is to calculate models with different number of factors and then inspect the models manually. This approach is time consuming, and the result may be biased because of the manual assessment of the model quality, making PARAFAC2 inaccessible for analytical chemists in general. Here, we develop a method that can determine an appropriate number of factors in an automated way. The automation is based on a number of model diagnostics (quality criteria) collected from models with different numbers of factors. Combining these diagnostics, it is possible to assess what the appropriate number of components is. In this work, only gas chromatography–mass spectrometry data are considered. However, it will most likely be fairly straightforward to expand the work to also cover liquid chromatography data (with a multivariate detector). Automating the model quality evaluation of the PARAFAC2 model enables both the inexperienced and trained user to perform comprehensive and advanced analysis of chromatographic data with a minimum of manual work. © 2013 The Authors. Journal of Chemometrics Published by John Wiley & Sons Ltd.     

Investigating the rapid diagnosis of gliomas from serum samples using infrared spectroscopy and cytokine and angiogenesis factors

The ability to diagnose brain cancer rapidly from serum samples is of great interest; such a diagnosis would allow for rapid testing and time to results providing a responsive diagnostic environment, ability to monitor treatment efficacy, early detection of recurrent tumours and screening techniques. Current methods rely upon subjective, time-consuming tests such as histological grading and are particularly invasive with the diagnostic test requiring hospitalisation of 2–3 days. A rapid diagnostic method based upon serum samples would allow for a relatively non-invasive test and open up the possibility of screening for brain cancer. We report for the first time the use of a Bioplex immunoassay to provide cytokine and angiogenesis factor levels that differ between serum from glioma and non-cancer patients specifically angiopoietin, follistatin, HGF, IL-8, leptin, PDGF-BB and PECAM-1 providing sensitivities and specificities as high as 88 % and 81 %, respectively. We also report, for the first time, the use of serum ATR-FTIR combined with a RBF SVM for the diagnosis of gliomas from non-cancer patients with sensitivities and specificities as high as 87.5 % and 100 %, respectively. We describe the combination of these techniques in an orthogonal diagnostic regime, providing strength to the diagnosis through data combinations, in a rapid diagnostic test within 5 h from serum collection (10 min for ATR-FTIR and 4 h for the Bioplex Immunoassay). This regime has the ability to revolutionise the clinical environment by providing objective measures for diagnosis allowing for increased efficiency with corresponding decreases in mortality, morbidity and economic impact upon the health services.

GC/MS of terpenes in walnut-tree leaves after accelerated solvent extraction

Terpenes, e. g. (+)-alpha-pinene, (-)-camphene, (-)-(-pinene, myrcene, R-(+)-limonene, eucalyptol, (+/-)-linalool, (-)-bornyl acetate, (-)-trans-caryophyllene, and alpha-humulene were determined in leaves of walnut trees from the Juglandaceae family (walnut tree, royal (J. regia L.), black (J. nigra L.), and Siebold (J. sieboldiana, var. Cordiformis Lam.) using gas chromatography with mass spectrometric detection. Terpenes were repeatedly (3 cycles, 5 min each) extracted from leaves of walnut trees by accelerated (pressurized) solvent extraction (ASE) 150 bar and 120 degrees C. The efficiency of ASE extraction was superior to that of steam distillation, solvent extraction according to Soxhlet, sonication, and extraction by agitation. Differences in relative concentrations and distribution of terpenes were studied in dependence on the species of walnut tree and on different locations.