Home About us Contact
|
Home About us Contact | ||
|
|
||
Pharmaceutical Compounds (pharmaceutical + compound)
Selected AbstractsPhysicochemical Properties of a New Multicomponent Cosolvent System for the pKa Determination of Poorly Soluble Pharmaceutical CompoundsHELVETICA CHIMICA ACTA, Issue 8 2007Abstract A mixture of cosolvents is described that significantly improves the solubility of most pharmaceutical compounds. The mixture consists of equal volumes of MeOH, 1,4-dioxane, and MeCN, thereby containing polar and nonpolar solvents, and is referred to as MDM (from MeOH, dioxane, and MeCN). MDM is mixed with H2O until the required composition is reached. The utility of this system is that it enables analytical measurements to be performed on a wide range of compounds where measurements would be impaired in aqueous solution. We present the physicochemical characteristics of MDM/H2O mixtures (density, dielectric constant, psKw) and the principles of pKa measurement in this solvent/H2O mixture. We also present pKa values in H2O of several drug compounds determined from values measured in MDM/H2O mixtures. [source] Palladium-Catalyzed Aerobic Oxidation of Naturally Occurring Allylbenzenes as a Route to Valuable Fragrance and Pharmaceutical CompoundsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 9 2010Luciana Abstract A palladium-catalyzed, aerobic oxidation of naturally occurring allylbenzenes, i.e., eugenol, methyleugenol, safrole, and estragole, in dimethylacetamide/water solutions under mild conditions has been developed, in which palladium(II) chloride is used in the absence of co-catalysts or special stabilizing ligands as the sole and recyclable catalyst. Methyl ketones that are important for the flavour and pharmaceutical industries have been obtained in good to excellent yields with low catalyst loadings (1,2,mol%) and high average turnover frequencies. This simple catalytic method represents an ecologically benign and economically attractive route to industrially valuable compounds starting from renewable substrates easily available from essential oils. [source] Multi-residue method for the analysis of pharmaceutical compounds in sewage sludge, compost and sediments by sonication-assisted extraction and LC determinationJOURNAL OF SEPARATION SCIENCE, JSS, Issue 12 2010Julia Martín Abstract A method for the simultaneous determination of 16 pharmaceutical compounds in three types of sewage sludge (primary, secondary and anaerobically digested dehydrated sludge), compost and sediment samples is described. Pharmaceutical compounds evaluated were nonsteroidal anti-inflammatory drugs (acetaminophen, diclofenac, ibuprofen, ketoprofen, naproxen and salicylic acid), antibiotics (sulfamethoxazole and trimethoprim), an anti-epileptic drug (carbamazepine), a ,-blocker (propranolol), a nervous stimulant (caffeine), estrogens (17,-ethinylestradiol, 17,-estradiol, estriol and estrone) and lipid regulators (clofibric acid, metabolite of clofibrate and gemfibrozil). The method is based on the ultrasonic-assisted extraction, clean-up by SPE and analytical determination by HPLC with diode array and fluorescence detectors. The best extraction recoveries were achieved in a three-step extraction procedure with methanol and acetone as extraction solvents. Extraction recoveries of several pharmaceutical compounds as caffeine were highly dependent on the type of sample evaluated. The applicability of the method was tested by analyzing primary, secondary and anaerobically digested dehydrated sludge, compost and sediment samples from Seville (Southern Spain). Ten of the sixteen pharmaceutical compounds were detected in sludge samples and five in compost and sediment samples. The highest concentration levels were recorded for ibuprofen in sewage samples, whereas salicylic acid and 17,-ethinylestradiol were detected in all of the samples analyzed. [source] Use of real-time FT-IR monitoring of a pharmaceutical compound under stress atmospheric conditions to characterize its solid-state degradation kineticsINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 1 2010Peter J. Skrdla The use of online FT-IR is described for investigating the degradation kinetics of the solid amorphous pharmaceutical compound, fosaprepitant dimeglumine (FD), under stress storage conditions (i.e., high temperature, T, and humidity, % RH). It is found that under conditions of elevated T and % RH, the kinetics are denucleation rate limited for the deliquescence of the amorphous FD solid, based on the high quality fits obtained to the authors' dispersive kinetic model for that mechanism. At elevated T and low % RH, it is found that a classical, first-order hydrolysis mechanism for the degradation of FD (which forms crystalline aprepitant, AP) significantly contributes to the overall conversion rate. That mechanism is similar to the one observed previously for the solution-phase hydrolysis of FD. Appropriate kinetic models are proposed for the FD-to-AP conversion under all of the experimental conditions investigated in this work. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 42: 25,36, 2010 [source] Direct analysis of pharmaceutical compounds in human plasma with chromatographic resolution using an alkyl-bonded silica rod columnRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2001Robert Plumb Monolithic columns have been successfully used with steep gradient and high flow rates for the direct analysis of a candidate pharmaceutical compound in human plasma. The monolithic columns showed excellent robustness with nearly 300 20-µL injections of plasma (diluted 1:1 with water) being made onto one column without significant deterioration in performance. The system gave excellent sensitivity with a limit of quantification of 5,ng/mL being achieved. Unlike previous methods of direct analysis the monolithic columns showed excellent resolution even after nearly 300 plasma injections. The column performance was measured before and after the analysis of the plasma samples. Copyright © 2001 John Wiley & Sons, Ltd. [source] Correction for QT/RR Hysteresis in the Assessment of Drug-Induced QTc Changes,Cardiac Safety of GadobutrolANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2009M.D., Marek Malik Ph.D. Background: The so-called thorough QT/QTc (TQT) studies required for every new pharmaceutical compound are negative if upper single-sided 95% confidence interval (CI) of placebo and baseline corrected QTc prolongation is <10 ms. This tight requirement has many methodological implications. If the investigated drug has a fast action and ECGs cannot be obtained at stable heart rates, QT/RR hysteresis correction is needed. Methods: This was used in a TQT study of gadobutrol. The TQT study was a randomized double-blind five-times crossover study of three doses of gadobutrol (0.1, 0.3, and 0.5 mmol/kg) that was placebo and positive effect controlled (moxifloxacin 400 mg). The study enrolled 50 healthy subjects with data of all periods. QT/RR hysteresis was assessed from prestudy exercise test ECGs. Among others, comparisons were made between population heart rate correction without hysteresis considerations and combined population heart rate and hysteresis correction. Results: The highest heart rate increase (placebo and baseline controlled) of 13.1 beats per minute (90% CI 9.9,16.4) occurred 1 minute after the administration of the highest dose of gadobutrol. Without hysteresis consideration, the highest ,,QTc were 9.91 ms (90% CI 8.01,11.81) while with hysteresis correction, these values were 7.62 ms (90% CI 6.37,8.87), thus turning a marginally positive TQT study into a negative finding. Conclusion: Hence, omitting hysteresis correction from episodes of fast heart rate changes may lead to incorrect conclusions. Despite substantial rate acceleration, accurate hysteresis correction confirms that gadobutrol does not have any effects on cardiac repolarization that would be within the limits of regulatory relevance. [source] Using Capsaicin Modified Multiwalled Carbon Nanotube Based Electrodes and p -Chloranil Modified Carbon Paste Electrodes for the Determination of Amines: Application to Benzocaine and LidocaineELECTROANALYSIS, Issue 23 2008Roohollah Abstract The utilization of the capsaicin modified carbon nanotube modified basal-plane pyrolytic graphite electrode or p -chloranil modified carbon paste electrodes are presented for the determination of pharmaceutical compounds containing amine functionality, such as benzocaine and lidocaine. In detection of benzocaine at a capsaicin modified electrode, the guaiacol functional group is irreversibly electrochemically oxidized to form the o -quinone derivative which then undergoes nucleophilic attack by the aromatic amine group in benzocaine via a 1,4-Michael addition mechanism forming a catechol-amine adduct. The electrochemically initiated formation of the capsaicin-benzocaine adduct causes a linear decrease in the voltammetric signal corresponding to capsaicin which correlates to the added concentration of benzocaine. [source] Comparison of dodecoxycarbonylvaline microemulsion, solvent-modified micellar and micellar pseudostationary phases for the chiral analysis of pharmaceutical compoundsELECTROPHORESIS, Issue 24 2005Melissa No abstracts. [source] Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubiaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2004Theodore B. Henry Abstract Contamination of surface waters by pharmaceutical chemicals has raised concern among environmental scientists because of the potential for negative effects on aquatic organisms. Of particular importance are pharmaceutical compounds that affect the nervous or endocrine systems because effects on aquatic organisms are possible at low environmental concentrations. Selective serotonin reuptake inhibitors (SSRIs) are drugs used to treat clinical depression in humans, and have been detected in low concentrations in surface waters. In this investigation, the acute and chronic toxicity of five SSRIs (fluoxetine, Prozac®; fluvoxamine, Luvox®; paroxetine, Paxil®; citalopram, Celexa®; and sertraline, Zoloft®) were evaluated in the daphnid Ceriodaphnia dubia. For each SSRI, the 48-h median lethal concentration (LC50) was determined in three static tests with neonate C. dubia, and chronic (8-d) tests were conducted to determine no-observable-effect concentrations (NOEC) and lowest-observable-effect concentrations (LOEC) for reproduction endpoints. The 48-h LC50 for the SSRIs ranged from 0.12 to 3.90 mg/L and the order of toxicity of the compounds was (lowest to highest): Citalopram, fluvoxamine, paroxetine, fluoxetine, sertraline. Mortality data for the 8-d chronic tests were similar to the 48-h acute data. The SSRIs negatively affected C. dubia reproduction by reducing the number of neonates per female, and for some SSRIs, by reducing the number of broods per female. For sertraline, the most toxic SSRI, the LOEC for the number of neonates per female was 0.045 mg/L and the NOEC was 0.009 mg/L. Results indicate that SSRIs can impact survival and reproduction of C. dubia; however, only at concentrations that are considerably higher than those expected in the environment. [source] Physicochemical Properties of a New Multicomponent Cosolvent System for the pKa Determination of Poorly Soluble Pharmaceutical CompoundsHELVETICA CHIMICA ACTA, Issue 8 2007Abstract A mixture of cosolvents is described that significantly improves the solubility of most pharmaceutical compounds. The mixture consists of equal volumes of MeOH, 1,4-dioxane, and MeCN, thereby containing polar and nonpolar solvents, and is referred to as MDM (from MeOH, dioxane, and MeCN). MDM is mixed with H2O until the required composition is reached. The utility of this system is that it enables analytical measurements to be performed on a wide range of compounds where measurements would be impaired in aqueous solution. We present the physicochemical characteristics of MDM/H2O mixtures (density, dielectric constant, psKw) and the principles of pKa measurement in this solvent/H2O mixture. We also present pKa values in H2O of several drug compounds determined from values measured in MDM/H2O mixtures. [source] Rapid screening and characterization of drug metabolites using a new quadrupole,linear ion trap mass spectrometerJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 2 2003Gérard Hopfgartner Abstract The application of a new hybrid RF/DC quadrupole,linear ion trap mass spectrometer to support drug metabolism and pharmacokinetic studies is described. The instrument is based on a quadrupole ion path and is capable of conventional tandem mass spectrometry (MS/MS) as well as several high-sensitivity ion trap MS scans using the final quadrupole as a linear ion trap. Several pharmaceutical compounds, including trocade, remikiren and tolcapone, were used to evaluate the capabilities of the system with positive and negative turbo ionspray, using either information-dependent data acquisition (IDA) or targeted analysis for the screening, identification and quantification of metabolites. Owing to the MS/MS in-space configuration, quadrupole-like CID spectra with ion trap sensitivity can be obtained without the classical low mass cutoff of 3D ion traps. The system also has MS3 capability which allows fragmentation cascades to be followed. The combination of constant neutral loss or precursor ion scan with the enhanced product ion scan was found to be very selective for identifying metabolites at the picogram level in very complex matrices. Owing to the very high cycle time and, depending on the mass range, up to eight different MS experiments could be performed simultaneously without compromising chromatographic performance. Targeted product ion analysis was found to be complementary to IDA, in particular for very low concentrations. Comparable sensitivity was found in enhanced product ion scan and selected reaction monitoring modes. The instrument is particularly suitable for both qualitative and quantitative analysis. Copyright © 2003 John Wiley & Sons, Ltd. [source] Evaluation of solution oxygenation requirements for azonitrile-based oxidative forced degradation studies of pharmaceutical compoundsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2006Eric D. Nelson Abstract AIBN and ACVA oxidative forced degradation models are examined for two drug molecules whose predominant oxidation chemistries arise from different reaction mechanisms (i.e., free radical vs. nucleophilic). Stress was conducted under a variety of initiator concentrations, and under ambient and pressurized oxygen atmospheres. In each case examined, the azonitrile initiator solutions served as a good predictive model of the major oxidative degradation products observed in pharmaceutical formulations. At low to moderate inititator concentrations, the degradation product distributions and degree of reactivity were similar for samples stored in ambient and pressurized oxygen environments. These results are rationalized with reference to the oxygen consumption kinetics of AIBN and ACVA solutions as a function of initiator concentration. The data suggests that ambient air provides sufficient oxygen to enable chain propagation of peroxy radicals in azonitrile solutions of concentrations appropriate to the forced degradation of pharmaceutical compounds. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1527,1539, 2006 [source] Prediction of the relaxation behavior of amorphous pharmaceutical compounds.JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2003Abstract Variability in the time to crystallization is a major technical and economic hurdle in using amorphous solids in dosage forms. It is hypothesized that amorphous solids "age", and that the older they are, the more relaxed they are and the higher the probability of crystallization. At present, there is no method that allows the "effective age" of an amorphous raw material to be assessed relative to its unrelaxed initial condition. A method has been developed that may satisfy this unmet need and provide a first step in subsequent investigation of the crystallization "event". This method consists of using master curves to enable the determination of the effective age (,aging') of an amorphous compound given normal excursions in storage conditions. The present study shows that master curves can be prepared for different storage conditions and subsequently be used to predict the relaxation or aging behavior of amorphous compounds with expected variations in storage conditions. Given the constraint that the system remain within the area enclosed by the equilibrium supercooled liquid line and the glass on the enthalpy,temperature diagram, experimental results using indomethacin and salicin as model compounds show that master curves can be used to predict aging behavior under nonisothermal conditions, with temperature excursions as large as 10°C. The nonisothermal relaxation behavior can be modeled by combining the Kohlrausch,Williams,Watts (KWW) stretched exponential function, the relaxation function, and a shift factor. In addition, a model was developed that extends the range of applicability to time/temperature regions in which partial crystallization occurs. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1464,1472, 2003 [source] Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopyJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2009Andrea Heinz Abstract Objectives Solid-state transformations may occur during any stage of pharmaceutical processing and upon storage of a solid dosage form. Early detection and quantification of these transformations during the manufacture of solid dosage forms is important since the physical form of an active pharmaceutical ingredient can significantly influence its processing behaviour, including powder flow and compressibility, and biopharmaceutical properties such as solubility, dissolution rate and bioavailability. Key findings Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most recently, terahertz pulsed spectroscopy have become popular for solidstate analysis since they are fast and non-destructive and allow solid-state changes to be probed at the molecular level. In particular, Raman and near-infrared spectroscopy, which require no sample preparation, are now commonly used coupled to fibreoptic probes and are able to characterise solid-state conversions in-line. Traditionally, uni- or bivariate approaches have been used to analyse spectroscopic data sets; however, recently the simultaneous detection of several solid-state forms has been increasingly performed using multivariate approaches where even overlapping spectral bands can be analysed. Summary This review discusses the applications of different vibrational spectroscopic techniques to detect and monitor solid-state transformations possible for crystalline polymorphs, hydrates and amorphous forms of pharmaceutical compounds. In this context, the theoretical basis of solid-state transformations and vibrational spectroscopy and common experimental approaches are described, including recent methods of data analysis. [source] Identification and characterization of pharmaceuticals using Raman and surface-enhanced Raman scatteringJOURNAL OF RAMAN SPECTROSCOPY, Issue 5 2004Pînzaru, S. Cînt Abstract Many recent papers reflect ongoing research and development concerning pharmaceutical applications of Raman techniques. This short review highlights different Raman techniques (dispersive, Fourier transform, resonance Raman, SERS, SERRS, FT-SERS) employed in pharmaceutical investigations. Several Raman applications such as fundamental structural investigations, quantitative analysis, drug,excipient interaction, formulation, limit of detection, pH-dependent pharmaceutical species, adsorption geometry at a given surface and functional groups involved in adsorption for several widely used pharmaceutical compounds are presented. Copyright © 2004 John Wiley & Sons, Ltd. [source] Multi-residue method for the analysis of pharmaceutical compounds in sewage sludge, compost and sediments by sonication-assisted extraction and LC determinationJOURNAL OF SEPARATION SCIENCE, JSS, Issue 12 2010Julia Martín Abstract A method for the simultaneous determination of 16 pharmaceutical compounds in three types of sewage sludge (primary, secondary and anaerobically digested dehydrated sludge), compost and sediment samples is described. Pharmaceutical compounds evaluated were nonsteroidal anti-inflammatory drugs (acetaminophen, diclofenac, ibuprofen, ketoprofen, naproxen and salicylic acid), antibiotics (sulfamethoxazole and trimethoprim), an anti-epileptic drug (carbamazepine), a ,-blocker (propranolol), a nervous stimulant (caffeine), estrogens (17,-ethinylestradiol, 17,-estradiol, estriol and estrone) and lipid regulators (clofibric acid, metabolite of clofibrate and gemfibrozil). The method is based on the ultrasonic-assisted extraction, clean-up by SPE and analytical determination by HPLC with diode array and fluorescence detectors. The best extraction recoveries were achieved in a three-step extraction procedure with methanol and acetone as extraction solvents. Extraction recoveries of several pharmaceutical compounds as caffeine were highly dependent on the type of sample evaluated. The applicability of the method was tested by analyzing primary, secondary and anaerobically digested dehydrated sludge, compost and sediment samples from Seville (Southern Spain). Ten of the sixteen pharmaceutical compounds were detected in sludge samples and five in compost and sediment samples. The highest concentration levels were recorded for ibuprofen in sewage samples, whereas salicylic acid and 17,-ethinylestradiol were detected in all of the samples analyzed. [source] Marfey's reagent: Past, present, and future uses of 1-fluoro-2,4-dinitrophenyl-5-L-alanine amideJOURNAL OF SEPARATION SCIENCE, JSS, Issue 1-2 2003Clayton B'Hymer Abstract This article describes some of the uses of Marfey's reagent, 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA), a pre-column derivatizing reagent for the separation of enantiomeric isomers of amino acids and amine compounds. An introduction to the basic implementation of this reagent and its historical development are presented. Actual uses in amino acid, short peptide, and pharmaceutical compounds are included, as well as the advantages and disadvantages over other pre-column derivatization techniques and direct chromatographic separations. Applications of current interest, including its use as an orthogonal analysis and in enantiomeric purity analysis of selenoamino acids using element specific detection, are also discussed. [source] Development and validation of the maximal electro-shock seizure model in dogsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2007P. R. TERRITO The development and validation of the maximal electro-shock (MES) model using phenobarbital (Pb) as the positive control is described. This approach builds on previous work in rodent model systems, and has been adapted to dogs as a tool for pharmaceutical dose selection. Dogs, like rodents, exhibit generalized convulsions which manifest as progressive clinical signs in a dose (electrical current) dependent fashion. At the limit (300 mA, 200 msec) animals underwent clonic-tonic convulsions consistent with complete generalized (Grand Mal) seizures with a grade 3 clinical score (CS) and a menace response time of 98.5 ± 24.4 sec (n = 8). Pretreatment of animals with Pb at 3, 10, and 30 mg/kg, in a 4-by-4 complete block crossover design (Latin-Square), resulted in a dose-dependant reduction in CS and menace response time. Estimates of plasma Pb concentration taken prior to MES induction showed a similar dose-dependent reduction in CS and menace response time with concentration. Using a cumulative logistic regression model, a predicted 50% probability of a CS = 1 was approximately 11.4 mg/kg. In addition, plasma Pb concentrations predicted a 50% probability of a CS = 1 occurs at plasma Pb concentration of approximately 16.0 ,g/mL. Combined these data suggest that MES is a useful model for evaluating generalized convulsions in canines and may provide a tool for dose selection of novel pharmaceutical compounds. [source] Comparison of bovine in vivo bioavailability of two sulfamethazine oral boluses exhibiting different in vitro dissolution profilesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2006M. N. MARTINEZ The bolus (or oblet) is a dosage form that can be used for the oral administration of pharmaceutical compounds to ruminating species. Unlike traditional tablets, oral boluses may contain quantities of drug on the order of grams rather than milligrams. Due to its size, it is only recently that USP-like in vitro dissolution methods have been developed for this dosage form. However, whether or not these dissolution tests can predict product in vivo performance has yet to be determined. The importance of this issue is apparent when the U.S. Food and Drug Administration Center for Veterinary Medicine is faced with the decision of whether to require additional in vivo bioequivalence study data to support the approval of changes in product chemistry or manufacturing method. The current study was undertaken to determine whether an in vivo/in vitro correlation can be established for bovine sulfamethazine oral boluses and to acquire insight into the magnitude of changes in in vitro product performance that can occur before corresponding changes are seen in in vivo blood level profiles. Based upon the results of this investigation, it is concluded that marked changes in in vitro sulfamethazine bolus performance can be tolerated before resulting in altered in vivo blood level profiles. However, the data also suggest that rumenal absorption may occur for some compounds. Therefore the degree to which variation in product in vitro dissolution profiles can be tolerated may be compound specific. [source] Improved detection of reactive metabolites with a bromine-containing glutathione analog using mass defect and isotope pattern matchingRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 9 2010André LeBlanc Drug bioactivation leading to the formation of reactive species capable of covalent binding to proteins represents an important cause of drug-induced toxicity. Reactive metabolite detection using invitro microsomal incubations is a crucial step in assessing potential toxicity of pharmaceutical compounds. The most common method for screening the formation of these unstable, electrophilic species is by trapping them with glutathione (GSH) followed by liquid chromatography/mass spectrometry (LC/MS) analysis. The present work describes the use of a brominated analog of glutathione, N -(2-bromocarbobenzyloxy)-GSH (GSH-Br), for the invitro screening of reactive metabolites by LC/MS. This novel trapping agent was tested with four drug compounds known to form reactive metabolites, acetaminophen, fipexide, trimethoprim and clozapine. Invitro rat microsomal incubations were performed with GSH and GSH-Br for each drug with subsequent analysis by liquid chromatography/high-resolution mass spectrometry on an electrospray time-of-flight (ESI-TOF) instrument. A generic LC/MS method was used for data acquisition, followed by drug-specific processing of accurate mass data based on mass defect filtering and isotope pattern matching. GSH and GSH-Br incubations were compared to control samples using differential analysis (Mass Profiler) software to identify adducts formed via the formation of reactive metabolites. In all four cases, GSH-Br yielded improved results, with a decreased false positive rate, increased sensitivity and new adducts being identified in contrast to GSH alone. The combination of using this novel trapping agent with powerful processing routines for filtering accurate mass data and differential analysis represents a very reliable method for the identification of reactive metabolites formed in microsomal incubations. Copyright © 2010 John Wiley & Sons, Ltd. [source] Reducing glycerophosphocholine lipid matrix interference effects in biological fluid assays by using high-turbulence liquid chromatographyRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 21 2008Lihong Du Matrix interferences can severely affect quantitative assays of biological samples when electrospray ionization (ESI) is employed with liquid chromatography/tandem mass spectrometry (LC/MS/MS). A major source of matrix interferences for plasma sample analyses is the presence of glycerophosphocholine (GPCho) lipids. The efficiency of online high-turbulence liquid chromatography (HTLC) extraction for eliminating these lipids is evaluated and the interfering effects of endogenous lipids on human plasma assays are measured for pharmaceutical compounds having a wide variety of chemical properties. It is found that GPCho lipids, represented by 16:0, 18:1 and 18:0 LPC (lysophosphatidylcholine) and 16:0-18:2 PC, cause variations for hydrophobic compound analyses even when optimal online HTLC extraction conditions are employed. The efficiency for lipid removal depends on the organic content of the transfer solvent, but turbulent flow loading has no significant effect. Copyright © 2008 John Wiley & Sons, Ltd. [source] Mass-directed fractionation and isolation of pharmaceutical compounds by packed-column supercritical fluid chromatography/mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 22 2001Tao Wang An automated packed-column semi-preparative supercritical fluid chromatography/mass spectrometry (SFC/MS) system incorporating mass-directed fraction collection has been designed and implemented as an alternative to preparative HPLC and preparative HPLC/MS (PrepLC/MS) for the purification of pharmaceutical compounds. The system incorporates a single quadrupole mass spectrometer and a supercritical fluid chromatograph. Separations were achieved using a binary solvent system consisting of carbon dioxide and methanol. Purification of SFC-separated compounds was achieved incorporating mass-directed fraction collection, enabling selective isolation of the target molecular weight compound and eliminating the collection of undesired compounds (e.g., by-products, excess starting materials, etc.). Cross contamination between fractions and recoveries of the system were investigated. Mass spectrometer ionization with basic mobile additives is discussed, and examples of preparative SFC/MS chiral separations are presented. Early experiences suggest SFC will be a powerful and complementary technique to HPLC for the purification of pharmaceutical compounds. Copyright © 2001 John Wiley & Sons, Ltd. [source] Direct analysis of pharmaceutical compounds in human plasma with chromatographic resolution using an alkyl-bonded silica rod columnRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2001Robert Plumb Monolithic columns have been successfully used with steep gradient and high flow rates for the direct analysis of a candidate pharmaceutical compound in human plasma. The monolithic columns showed excellent robustness with nearly 300 20-µL injections of plasma (diluted 1:1 with water) being made onto one column without significant deterioration in performance. The system gave excellent sensitivity with a limit of quantification of 5,ng/mL being achieved. Unlike previous methods of direct analysis the monolithic columns showed excellent resolution even after nearly 300 plasma injections. The column performance was measured before and after the analysis of the plasma samples. Copyright © 2001 John Wiley & Sons, Ltd. [source] Use of affinity capillary electrophoresis for characterizing pharmaceutical colloidal vehicle systems thermodynamicallyBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7-8 2001Neubert Reinhard Abstract This review offers a detailed discussion of the interaction between pharmaceutical compounds and vehicles using the affinity capillary electrophoresis and the microemulsion electrokinetic chromatography. Partition coefficients of drugs were calculated between a micelle and an aqueous phases from the measurement of the migration time, provided the critical micelle concentration and the phase ratio are known. Thermodynamic quantities such as enthalpy and entropy changes of micellar solubilization were calculated from the temperature dependence of the partition coefficients. Partial specific volumes were measured using dynamic light scattering. The logarithm of the partition coefficients and the capacity factor in the micellar system were correlated with the logarithm of the n-octanol/water partition coefficients. Copyright © 2001 John Wiley & Sons, Ltd. [source] Recent progress in engineering ,/, hydrolase-fold family membersBIOTECHNOLOGY JOURNAL, Issue 2 2007Zhen Qian Abstract The members of the ,/, hydrolase-fold family represent a functionally versatile group of enzymes with many important applications in biocatalysis. Given the technical significance of ,/, hydrolases in processes ranging from the kinetic resolution of enantiomeric precursors for pharmaceutical compounds to bulk products such as laundry detergent, optimizing and tailoring enzymes for these applications presents an ongoing challenge to chemists, biochemists, and engineers alike. A review of the recent literature on ,/, hydrolase engineering suggests that the early successes of "random processes" such as directed evolution are now being slowly replaced by more hypothesis-driven, focused library approaches. These developments reflect a better understanding of the enzymes' structure-function relationship and improved computational resources, which allow for more sophisticated search and prediction algorithms, as well as, in a very practical sense, the realization that bigger is not always better. [source] Polymer Fibers as Carriers for Homogeneous CatalystsCHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2007Michael Stasiak Abstract This paper describes a polymer fiber-based approach for the immobilization of homogeneous catalysts. The goal is to generate products that are free of catalysts which would be of great importance for the development of optoelectronic or pharmaceutical compounds. Electrospinning was employed to prepare the non-woven fiber assembly composed of polystyrene. The homogeneous catalyst scandium triflate was immobilized on the polystyrene fibers during electrospinning and on corresponding core shell fibers using a fiber template approach. An imino aldol and an aza-Diels,Alder model reaction were carried out with each fibrous catalytic system. This resulted in the immobilization of homogeneous catalysts in a polymer environment without loss of their catalytic activity and may even be enhanced when compared with reactions carried out in homogeneous solutions. [source] Molecular modeling of chiral-modified zeolite HY employed in enantioselective separationCHIRALITY, Issue 6 2007Siricharn S. Jirapongphan Abstract Insight into enantioselective separation utilizing chiral-modified zeolite HY could be useful in designing a chiral stationary phase for resolving pharmaceutical compounds. A model was employed to better understand the enantioseparation of valinol in zeolite HY that contains (+)-(1R;2R)-hydrobenzoin as a chiral modifier. This model incorporates the zeolite support and accounts for the flexible change. Results from grand canonical Monte Carlo and molecular dynamics simulations indicate that the associated diastereomeric complex consists of a single (+)-(1R;2R)-hydrobenzoin and a single valinol molecules located in the zeolite HY supercage. Supercage-based docking simulation predicted an enantioselectivity of 2.6 compared with that of 1.4 measured experimentally. Also, the supercage-based docking simulation demonstrated a single binding motif in the S complex, and two binding motifs in the R complex. The multiple binding modes in the R complex resulted in its lower stability. This is hypothesized to be the origin of the weaker binding between (,)-(R)-valinol and the chiral modifier, and explains why (+)-(R)-valinol is retained more in the chiral-modified zeolite system studied. Chirality, 2007. © 2007 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||