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Drug adsorption on poly(acrylic acid) grafted membrane
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Drug adsorption cm poly(nerylic acid) grafted membrane S.Akerman’, P.Koivu’, K.Akerman’, A.Roos’and P.Paronen’ ‘Department of Pharmaceutics, University of Kuopio, P.O.BOX 1627,702ll Kuopio, Finland 2Depatment of Clinical Chemistry, Kuopio University Hospital ‘Department of Polymer Technology, Abo Akademi University
DETERMINATION AND ZIN’C IN WORKERS
Poly(acrylic acid) grafted poly(vinylidene fluoride) (PVDF-PAA) membrane is a porous, pH sensitive membrane, which is cation selective due to the partial ionization of carboxyl groups. At pHs above the pK, value of PAA (-4). dissociated carboxyl groups are able to adsorb cationic drugs. In present study, effects of pH and albumin on drug adsorption rate where studied using thioridazine and desipramine as model drugs. 20 wP/o grafted PVDF-PAA membrane was incubated in 5 pglml drug solutions and samples were collected during 24 h. Drug concentrations were measured by HPLC. Drug adsorption onto the membrane increase significantly at higher pH values, when carboxylic acid groups of the membrane are dissociated and drug is fully ionized. Adsorption rate of SO-100% is achieved during 5 hrs. In the presence of albumin, adsorption rate was significantly decreased.
OF LEAD, CADMIUM, COPPER HAIR OF SICK AND HEALTHY
M.H. Borawska ‘, A. Oltanewska ‘, K. Hukalowicz ’ Laboratory of Bromatology and * Department Health, Medical University, Kilinsk~ I, 15-230 Poland
’ of Public Bialystok,
Lead (Pb) and cadmium (Cd) are the most prevalent toxic metals and concern over its deleterious effects on humans has increased in recent years The majority of trace elements as such copper (Cu) and zinc (Zn) play an important role as co-factors in highly varying enzyme reaction in the organism. Because the hour analysis can provide valuable Information in the case of systematic intoxication, we decided to determine Pb, Cd, Cu. Zn in head hair of sick and healthy workers. The content of heavy metals and trace elements were determined by atomic absorption spectrometry in men aged 45-55 years. The studied two groups of workers: 84 healthy men and 89 men mainly with gastrointestinal and cardiovascular diseases. With regard to Pb, Cd, Cu and Zn content in hair, no differences were observed between sick and healthy workers. In contrast, workers with the higher body mass index @MI) had more concentration of cadmium (@g) m hair BMI<25=0.3931; 2530=140
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SYNERGY AMONG X-RAY CRYSTALLOGRAPHY, MOLECULAR MODELING, THERMAL ANALYSIS, SPECTROSCOPIC AND CHEMOMETRIC METHODS IN THE STUDY OF RIFAMYCINS ACTIVITY AND POLYMORPHISM
ANALYSIS AND PHAHMACOKINETICS OF CLOZAPINE IN PLASMA OF SCHIZOPHRENIC PATIENTS
A. Bactia, G. Pelizzia, P. Ferrarib and M. NebulonibJ a) Dipartimento di Chimica Generale ed Inorganica, University of Parma, V. delle Scienze, l-431 00 Parma, Italy b) Lepetit Research Center, Via R. Lepetit, 34- I 21040 Gerenzano (VA), Italy. C Present address: Redox snc, Via SMargherita, 51 - I-20093 Cologno Mse (Ml), Italy. Rifamycins are naphthalenic ansamycins which exert their antibiotic activity by specific Inhibition of bacterial DNAdependent RNA polymerase. Qualitative requirements for activity involve the presence of a specific arrangement of oxygen atoms on active rifamycins. In order to characterise quantitatively this model, the support of structural data is needed. Several X-ray structural studies on a series of active and non-active rtfamycin derivatives have been reported in literature in the past thirty years. NMR experiments indicated that the portions of the rifamycin molecule responsible for activity are invariant on passing from solid-state to solution. In the present work chemiometric methods are used to identify which structural parameters are statistically most correlated with activity. Based on X-ray, IR and NMR data, a mechanism of structural rearrangement from active into nonactive conformation is studied by molecular modeling techniques. Thermochemical data are used to correlate conformational variety to polymorphism.
F. Bugamelli-l, M.A. Raggil, D. De Ron&?, V. Volterraz. G. Cantelli For@ ‘Department of Pharmaceutical Sciences, 2Psicbiatric Cliic and ‘Department of Pharmacology,University of Bologna - ITALY Clozapine ( 8-cbloro-ll-(4-methyl-l-pipe.razinyl)-5Hdibenzoenzo[b,el[ 1,4]-diazepine is considerable the drug of choice for patients who are non/poor responders to the traditional neuroleptic drugs, and for patients who are at risk of potential extrapyramidal effects. It can, in turn, cause several other dangerous side effects, such as a reversible agranulocytosis and episodes of epilepsy, during which high levels of clozapine were found in the plasma of patients. The need for accurate monitoring of clozapine plasma levels in patients treated with the drug is, therefore, apparent; suitable analytical methods, must be highly sensitive and selective. A bighperformance liquid chromatograpbic method with amperometric detection has been developed for the determination of levels of clozapine and its active metabolite N-desmethylclozapine in human plasma. An accurate solid-phase extraCtion (SPE) procedure was used to extract the clozapines from plasma samples. The analysis was performed on a C8 reversed phase column (150x4.6 mm I.D., 5 pm), with acetonitrile-phosphate buffer (PH 3.5), as the mobile phase. The detection voltage was +800 mV. Linear responses were obtained between 2 n&L and 100 n&nL of clozapines. It has the advantages of requiring a minimal volume of blood (100 pL) for one analysis; for that it has been utilized for a pharmacokinetics study, which is now in progress.
161
163
Drug adsorption cm poly(nerylic acid) grafted membrane S.Akerman’, P.Koivu’, K.Akerman’, A.Roos’and P.Paronen’ ‘Department of Pharmaceutics, University of Kuopio, P.O.BOX 1627,702ll Kuopio, Finland 2Depatment of Clinical Chemistry, Kuopio University Hospital ‘Department of Polymer Technology, Abo Akademi University
DETERMINATION AND ZIN’C IN WORKERS
Poly(acrylic acid) grafted poly(vinylidene fluoride) (PVDF-PAA) membrane is a porous, pH sensitive membrane, which is cation selective due to the partial ionization of carboxyl groups. At pHs above the pK, value of PAA (-4). dissociated carboxyl groups are able to adsorb cationic drugs. In present study, effects of pH and albumin on drug adsorption rate where studied using thioridazine and desipramine as model drugs. 20 wP/o grafted PVDF-PAA membrane was incubated in 5 pglml drug solutions and samples were collected during 24 h. Drug concentrations were measured by HPLC. Drug adsorption onto the membrane increase significantly at higher pH values, when carboxylic acid groups of the membrane are dissociated and drug is fully ionized. Adsorption rate of SO-100% is achieved during 5 hrs. In the presence of albumin, adsorption rate was significantly decreased.
OF LEAD, CADMIUM, COPPER HAIR OF SICK AND HEALTHY
M.H. Borawska ‘, A. Oltanewska ‘, K. Hukalowicz ’ Laboratory of Bromatology and * Department Health, Medical University, Kilinsk~ I, 15-230 Poland
’ of Public Bialystok,
Lead (Pb) and cadmium (Cd) are the most prevalent toxic metals and concern over its deleterious effects on humans has increased in recent years The majority of trace elements as such copper (Cu) and zinc (Zn) play an important role as co-factors in highly varying enzyme reaction in the organism. Because the hour analysis can provide valuable Information in the case of systematic intoxication, we decided to determine Pb, Cd, Cu. Zn in head hair of sick and healthy workers. The content of heavy metals and trace elements were determined by atomic absorption spectrometry in men aged 45-55 years. The studied two groups of workers: 84 healthy men and 89 men mainly with gastrointestinal and cardiovascular diseases. With regard to Pb, Cd, Cu and Zn content in hair, no differences were observed between sick and healthy workers. In contrast, workers with the higher body mass index @MI) had more concentration of cadmium (@g) m hair BMI<25=0.3931; 25
162
164
SYNERGY AMONG X-RAY CRYSTALLOGRAPHY, MOLECULAR MODELING, THERMAL ANALYSIS, SPECTROSCOPIC AND CHEMOMETRIC METHODS IN THE STUDY OF RIFAMYCINS ACTIVITY AND POLYMORPHISM
ANALYSIS AND PHAHMACOKINETICS OF CLOZAPINE IN PLASMA OF SCHIZOPHRENIC PATIENTS
A. Bactia, G. Pelizzia, P. Ferrarib and M. NebulonibJ a) Dipartimento di Chimica Generale ed Inorganica, University of Parma, V. delle Scienze, l-431 00 Parma, Italy b) Lepetit Research Center, Via R. Lepetit, 34- I 21040 Gerenzano (VA), Italy. C Present address: Redox snc, Via SMargherita, 51 - I-20093 Cologno Mse (Ml), Italy. Rifamycins are naphthalenic ansamycins which exert their antibiotic activity by specific Inhibition of bacterial DNAdependent RNA polymerase. Qualitative requirements for activity involve the presence of a specific arrangement of oxygen atoms on active rifamycins. In order to characterise quantitatively this model, the support of structural data is needed. Several X-ray structural studies on a series of active and non-active rtfamycin derivatives have been reported in literature in the past thirty years. NMR experiments indicated that the portions of the rifamycin molecule responsible for activity are invariant on passing from solid-state to solution. In the present work chemiometric methods are used to identify which structural parameters are statistically most correlated with activity. Based on X-ray, IR and NMR data, a mechanism of structural rearrangement from active into nonactive conformation is studied by molecular modeling techniques. Thermochemical data are used to correlate conformational variety to polymorphism.
F. Bugamelli-l, M.A. Raggil, D. De Ron&?, V. Volterraz. G. Cantelli For@ ‘Department of Pharmaceutical Sciences, 2Psicbiatric Cliic and ‘Department of Pharmacology,University of Bologna - ITALY Clozapine ( 8-cbloro-ll-(4-methyl-l-pipe.razinyl)-5Hdibenzoenzo[b,el[ 1,4]-diazepine is considerable the drug of choice for patients who are non/poor responders to the traditional neuroleptic drugs, and for patients who are at risk of potential extrapyramidal effects. It can, in turn, cause several other dangerous side effects, such as a reversible agranulocytosis and episodes of epilepsy, during which high levels of clozapine were found in the plasma of patients. The need for accurate monitoring of clozapine plasma levels in patients treated with the drug is, therefore, apparent; suitable analytical methods, must be highly sensitive and selective. A bighperformance liquid chromatograpbic method with amperometric detection has been developed for the determination of levels of clozapine and its active metabolite N-desmethylclozapine in human plasma. An accurate solid-phase extraCtion (SPE) procedure was used to extract the clozapines from plasma samples. The analysis was performed on a C8 reversed phase column (150x4.6 mm I.D., 5 pm), with acetonitrile-phosphate buffer (PH 3.5), as the mobile phase. The detection voltage was +800 mV. Linear responses were obtained between 2 n&L and 100 n&nL of clozapines. It has the advantages of requiring a minimal volume of blood (100 pL) for one analysis; for that it has been utilized for a pharmacokinetics study, which is now in progress.