Andrei Medvedovici

Degradation of pharmaceutical compound pentoxifylline in water by non-thermal plasma treatment.

The decomposition of a model pharmaceutical compound, pentoxifylline, in aqueous solution was investigated using a dielectric barrier discharge (DBD) in coaxial configuration, operated in pulsed regime, at atmospheric pressure and room temperature. The solution was made to flow as a film over the surface of the inner electrode of the plasma reactor, so the discharge was generated at the gas-liquid interface. Oxygen was introduced with a flow rate of 600sccm. After 60min plasma treatment 92.5% removal of pentoxifylline was achieved and the corresponding decomposition yield was 16g/kWh. It was found that pentoxifylline degradation depended on the initial concentration of the compound, being faster for lower concentrations. Faster decomposition of pentoxifylline could be also achieved by increasing the pulse repetition rate, and implicitly the power introduced in the discharge, however, this had little effect on the decomposition yield. The degradation products were investigated by liquid chromatography-mass spectrometry technique (LC-MS). The evolution of the intermediates during plasma treatment showed a fast increase in the first 30min, followed by a slower decrease, so that these products are almost completely removed after 120min treatment time.

Chiral packed column subcritical fluid chromatography on polysaccharide and macrocyclic antibiotic chiral stationary phases

Abstract The polysaccharide chiral stationary phases (CSPs) Chiralcel OD and Chiralpak AD, and the macrocyclic antibiotic CSPs Chirobiotic V and Chirobiotic T were evaluated in packed column subcritical fluid chromatography (pSFC) for the separation of different types of racemic compounds (β-blockers, β-agonists, benzodiazipines, non-steroidal anti-inflammatory drugs, barbiturates, free and derivatized amino acids, etc.). The same conditions and program could be applied to check the applicability and enantioselectivity of one of the CSPs for a given racemic mixture. The conditions are: temperature 30°C, pressure 200 bar, flow-rate 2 ml/min, carbon dioxide, modifier methanol containing 0.1% trifluoroacetic acid (TFAA) and 0.1% triethylamine (TEA) with a gradient from 5% (5 min) to 30% at 5%/min. A resolution of 0.4 under those conditions generally indicates that baseline separation can be realized on the CSP by fine-tuning the different parameters of the SFC separation. The best CSP for pSFC proved to be Chiralpak AD which provided separation for 70% of the 44 substances tested, followed by Chiralcel OD (66%), Chirobiotic T (50%) and Chirobiotic V (48%). For comparison, the enantio-selectivity in pSFC of the brush type CSPs Chirex 3022 with π-donor characteristics and Chirex 3005 with π-acceptor characteristics was also evaluated. As expected, these phases perform poorly under SFC conditions, on Chirex 3022 (34%) and on Chirex 3005 (20%).

Degradation of antibiotics in water by non-thermal plasma treatment

The decomposition of three β-lactam antibiotics (amoxicillin, oxacillin and ampicillin) in aqueous solution was investigated using a dielectric barrier discharge (DBD) in coaxial configuration. Solutions of concentration 100 mg/L were made to flow as a film over the surface of the inner electrode of the plasma reactor, so the discharge was generated at the gas-liquid interface. The electrical discharge was operated in pulsed regime, at room temperature and atmospheric pressure, in oxygen. Amoxicillin was degraded after 10 min plasma treatment, while the other two antibiotics required about 30 min for decomposition. The evolution of the degradation process was continuously followed using liquid chromatography-mass spectrometry (LC-MS), total organic carbon (TOC) and chemical oxygen demand (COD) analyses.

Characterization of triglycerides in vegetable oils by silver-ion packed-column supercritical fluid chromatography coupled to mass spectroscopy with atmospheric pressure chemical ionization and coordination ion spray.

Characterization of triglycerides in vegetable oils was achieved by silver-ion packed-column supercritical fluid chromatography (SI-pSFC) with mass spectrometric detection. Hyphenation was made using commercially available liquid chromatography-mass spectrometry (LC-MS) interfaces without any modification. A make-up fluid was delivered through a T-piece placed before or after the SFC restrictor by means of a high pressure pump. Atmospheric pressure chemical ionization (APCI) and coordination ion spray (CIS) with silver ions were used as ionization modes. Compared to UV detection, the sensitivity was increased by a factor of 100. Both ionization modes are generating similar structural information. Molecular ions [M-H]+ or [M-Ag(-)] are observed in the mass spectra with exception of the saturated triglycerides for which only CIS gives intense molecular ions. The position at which the fatty acids are esterified to the glycerol backbone can be elucidated by pSFC-APCI although it remains speculative whether this is valid for highly unsaturated triglycerides because reference compounds are not available to proof this.

HPLC-DAD determination of Metformin in human plasma using derivatization with p-nitrobenzoyl chloride in a biphasic system

An optimized method for determination of Metformin at ppb level in human plasma is described. Derivatization of Metformin with p-nitrobenzoyl chloride was carried out in a biphasic system. The derivative extracted in the organic layer (dichloromethane) was concentrated and analyzed by HPLC-DAD, using an isocratic elution (water/methanol mixture 65/35), monitored at 280 nm. Good selectivity against co-extracted matrix components was observed. A detection limit of 10 ppb Metformin in human plasma was reached.

Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review

Undoubtedly, the use of oximes represents real progress in counteracting intoxications with organophosphates (OP), through potentiating antidotal effects of atropine. The penetration extent of these compounds through the blood–brain barrier (BBB) to significantly reactivate phosphorylated or phosphonylated acetylcholinesterase (AChE) in the brain still remains a debatable issue. Penetration of biological barriers by oximes was investigated mainly through determination of several quantitative parameters characterizing digestive absorption and BBB penetration. A weak penetration of biological barriers could be concluded from the available experimental data. The functional parameters/therapeutic effects following the penetration of oximes through BBB, more precisely the antagonism of OP‐induced seizures and hypothermia, prevention of brain damage and respiratory center protection, leading to the final end‐point, the survival of intoxicated organisms, are of high interest. It seems obvious that oximes are weakly penetrating the BBB, with minimal brain AChE reactivation (<5%) in important functional areas, such as the ponto‐medullar. The cerebral protection achieved through administration of oximes is only partial, without major impact on the antagonism of OP‐induced seizures, hypothermia and respiratory center inhibition. The antidotal effects probably result from synergic effects of other PD properties, different from the brain AChE reactivation process. Oxime structures especially designed for enhanced BBB penetration, through potentiating the hydrophobic characteristics, more often produce neurotoxic effects. Certainly, obtaining oximes with broad action spectrum (active against all OP types) would make a sense, but certainly, such a target is not achievable only through the increase in their penetrability in the brain.

SYNTHESIS AND PAIRING PROPERTIES OF OLIGONUCLEOTIDES CONTAINING 3-HYDROXY-4-HYDROXYMETHYL-1-CYCLOHEXANYL NUCLEOSIDES

Cyclohexanyl nucleic acid (CNA) represents a novel enantioselective Watson–Crick base-pairing system. Homochiral oligomers of equivalent chirality show antiparallel Watson–Crick pairing, while those of opposite sense do not. D-CNA hybridizes with natural nucleic acids, preferentially with RNA. A conformational change involving chair inversion is expected to occur upon duplex formation (A→B).

Validation of a LC-fluorescence method for determination of free captopril in human plasma, using a pre-column derivatization reaction with monobromobimane

Both derivatization of free captopril in human plasma samples using monobromobimane as fluorescent label and the corresponding HPLC-fluorescence detection (FLD) method were validated. Calibration curve for the fluorescent captopril derivative in plasma samples is linear in the ppb-ppm range with a detection limit of 4 ppb and an identification limit of 10 ppb (P%: 90; nu > or = 5). These methods were successfully applied on bioequivalence studies carried out on some marketed pharmaceutical formulations.

Application of chiralcel OJ in supercritical fluid chromatography for the resolution of different groups of frequently used drug racemates

Supercritical fluid chromatography was applied to evaluate the direct chiral discriminative properties of Chiralcel OJ, a tris(4-methylbenzoate) cellulose column towards frequently administered drugs. Two groups of acidic drugs, profen and barbiturate derivatives, and a few basic drugs of the benzodiazepine type were analysed. The effect on enantioselectivity of carbon dioxide when using methanol are acetonitrile as primary modifier was studied. Acetonitrile proved to be a good alternative for methanol, especially for the profen compounds that were not well resolved using methanol. The results were compared to normal phase chromatographic applications on the same column. SFC was not necessarily superior to high-performance liquid chromatography. Chirality 9:126–132, 1997.

Liquid extraction and HPLC-DAD assay of hydrochlorothiazide from plasma for a bioequivalence study at the lowest therapeutic dose

SummaryThe main parameters considered in optimizing the liquid extraction and quantitative assay were the yield, precision, limit of quantification, time required for extraction and concentration, and quantity of solvent. The influence on these parameters of the following factors was examined: nature of the extracting solvent, quantity of solvent, co-extraction solvent, and duration of stirring. Instead of equilibrium parameters of the involved thermodynamic system, a kinetic approach was preferred in terms of the effective partition ‘constant’, which is not really constant but a function of time and extraction conditions. The final selected method, considered to be rapid and simple, was applied to determine the pharmacokinetics of hydrochlorotiazide (HCT) after administration of Capozide (Bristol-Myers Squibb) tablets containing 50 mg Captopril and 25 mg HCT, to 4 healthy volunteers. The results obtained were in accordance with the pharmacokinetic parameters of HCT reported in the literature.