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Toxicological analysis of aluminum in drinking waters and dialysis solutions
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DETERMINATION OF IMMUNOSUPPRESSIVE DRUGS IN SERUM OF RENAL TRANSPLANT PATIENTS USING MICELLAR ELECTROKINETIC CHROMATOGRAPHY u’, Bbhler, 3.2, Keller, E.2, Frahm, A. W.’ ’Chair of Pharmaceutical Chemistry, University of Freiburg, Hermann-Herder-&. 9; D-79104 Freiburg im Breisgau, Germany 2 Department of Nephrology, University of Freiburg, Hugstetter Str. 55; D-79106 Freiburg im Breisgau, Germany
ANALYSIS OF ANTITUMOR VINBLASTINE AND VINCRISTINE ALKALOIDS BY ESllMSlMS A. Piovan, R. Filippini, D. Favretlo’. R. Caniato and G. Innocenti” Departmentof Biology,Via U. Bassi. 5818.35131 Padova, Italy ‘CNR, Area di Ricerca,Corso Stati Uniti. 4, 35100 Padova, Italy “Department of Pharmaceutical Sciences, Via Matzolo. 5. 35131 Padova, Italy.
Prednisolone, cyclosporin A and mycophenolate mofetil are used in the immunosuppressive drug regimen fohowing renal transplantation. The first two drugs were determined using solid phase extraction and micellar electrokinetic chromatography (MECC). Prednisolone serum levels were monitored during several hours after administration and concentration / time curves were elaborated. Mycophenolic acid, the active moiety of mycophenolate mofetil, was determined without any pretreatment using direct serum injection technique (DSI-MBCC). All separations took place in fused silica capillaries using a phosphate / borate buffer pH 8.0 (20 mM) with 50 mM sodiumdodecylsulfate as micelle forming agent and 16 % (v/v) acetonitrile as organic modifier. Detection was performed at )i= 254 run (prednisolone and mycophenolic acid) and at h= 210 nm (cyclosporin A).
Electrospray ionization (ESI) mass spectrometty (MS) has recently become one of the most powerful analytical approaches for the study of polar, thermolabile, large compounds and has therefore found widespread applications. In particular, one of its most appreciated feature is the easy linking with HPLC, which has made HPLClESllMS of large use in biochemical and medical application fields. We thought of interest to apply this analytical methodology to the study of the two antitumor alkaloids of Cafharanfhus roseus. ESI mass spectrometry of vinblastine and vincristine lead to significant mass spectra providing not only information on the molecular weight of the two alkaloids but also characteristic fragmentation patterns which will result useful when the identification of these alkaloids is required and will improve the specificity of analytical methods such as those based on HPLC quantifications of antitumor alkaloids at low levels.
Lit; No&S., Bohler,J., Keller,E., Frahm,A.W.: - Poster at 1.Burop.Gmd.Stud.Meeting: Pharmazie 53(3),29(1998) - J.Pharm.Biomed.AnaJ. 1998 (in press)
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DETERMINATION OF MYCOPHENOLIC ACID IN HUMAN PLASMA BY HPLC
TOXICOLOGICAL ANALYSIS OF ALUMINUM IN DRINKING WATERS AND DIALYSIS SOLUTIONS
Pawinski T., Paruszewski R. Department of Drug Chemistry, Medical Academy, 1 Banacha Str., 02097 Warsaw, Poland. Mvcoohenolic acid IMPAI is the active metabolite of the immunosuppressive drug mycophenolate mofetil. We report a rapid HPLC - UV method for the determination of MPA in plasma. Plasma samples 0,5 ml with oxazepam added as internal standard /IS/ were extracted by BakerBond Cl8 solid phase extraction. 0,05 ml is injected into the Nova-Pak Cl8 column. Mobile phase consisted of 45% acetonitrilel 55% phosphoric acid I O,Oti%, v/v I at a flow rate 0.8 mllmin. Absorbance is measured at 254 nm. The retention times of MPA and IS were 3,6 and 25 min respectiily. The limit of detection was 0.5 mg/L. Recovery over the linear concentration range 0,5-20,O mg/l_ was about 90% with the CV 7,0%. Accuracy at 0,5 mg/L and 20 mg/L were 94% and 97% respecttvely. This method can be applied for therapeutic drug monitoring of mycophenolic acid in plasma.
M.A. Raqqi’, R. Mandrioli’, C. Sabbioni’, F. Bugamelli’ and G. Cantelli Forti” ??Department of Pharmaceutical Sciences, Via Belmeloro, 6, 40126 Bologna, Italy; * Department of Pharmacology, Via Imerio, 46, 40126 Bologna, Italy. Aluminum at trace levels (ppb) is a common contaminant of hemodialysis solutions; it can be responsible for severe illnesses in patients suffering from chronic renal failure who need long-term hemodialysis treatments. Chronic aluminum toxicity manifests itself with anemia, bone diseases, encephalopathiir and a neurological illness known as “dialysis dementia”. Aluminum toxicity originates from its accumulation in the bone and in the CNS; for this reason, Al has been recently associated to Alzheimer’s disease. Epidemiologiccll studies found a correlation between Mgh levels of Al in drinking waters and an high incidence of Alzheimer’s syndrome in the population. The need for a reliable method for Al determination in drinking waters and in dialysis solutions is thus apparent. The accurate and sensitive rpectrofluorimetric procedure developed employs Mordant Red 19 as a complexing reagent. After thermostatting at 70°C for 60 minutes, the emission of the fluorescent metal chelate was measured at 558 nm, exdting at 478 nm. The method shows a good linearity over the 1.0 - 80 ppb range. The limit of quantkatbn (LOQ) was 1.0 ppb, while the limit of detectton (LOD) was 0.5 ppb. It was found that an extractive step with an organic solvent gives hiiher sensittvity to the method, which proved to be suitable for the determination of aluminum in commercial dialysis fluids and in mineral waters.
177
179
DETERMINATION OF IMMUNOSUPPRESSIVE DRUGS IN SERUM OF RENAL TRANSPLANT PATIENTS USING MICELLAR ELECTROKINETIC CHROMATOGRAPHY u’, Bbhler, 3.2, Keller, E.2, Frahm, A. W.’ ’Chair of Pharmaceutical Chemistry, University of Freiburg, Hermann-Herder-&. 9; D-79104 Freiburg im Breisgau, Germany 2 Department of Nephrology, University of Freiburg, Hugstetter Str. 55; D-79106 Freiburg im Breisgau, Germany
ANALYSIS OF ANTITUMOR VINBLASTINE AND VINCRISTINE ALKALOIDS BY ESllMSlMS A. Piovan, R. Filippini, D. Favretlo’. R. Caniato and G. Innocenti” Departmentof Biology,Via U. Bassi. 5818.35131 Padova, Italy ‘CNR, Area di Ricerca,Corso Stati Uniti. 4, 35100 Padova, Italy “Department of Pharmaceutical Sciences, Via Matzolo. 5. 35131 Padova, Italy.
Prednisolone, cyclosporin A and mycophenolate mofetil are used in the immunosuppressive drug regimen fohowing renal transplantation. The first two drugs were determined using solid phase extraction and micellar electrokinetic chromatography (MECC). Prednisolone serum levels were monitored during several hours after administration and concentration / time curves were elaborated. Mycophenolic acid, the active moiety of mycophenolate mofetil, was determined without any pretreatment using direct serum injection technique (DSI-MBCC). All separations took place in fused silica capillaries using a phosphate / borate buffer pH 8.0 (20 mM) with 50 mM sodiumdodecylsulfate as micelle forming agent and 16 % (v/v) acetonitrile as organic modifier. Detection was performed at )i= 254 run (prednisolone and mycophenolic acid) and at h= 210 nm (cyclosporin A).
Electrospray ionization (ESI) mass spectrometty (MS) has recently become one of the most powerful analytical approaches for the study of polar, thermolabile, large compounds and has therefore found widespread applications. In particular, one of its most appreciated feature is the easy linking with HPLC, which has made HPLClESllMS of large use in biochemical and medical application fields. We thought of interest to apply this analytical methodology to the study of the two antitumor alkaloids of Cafharanfhus roseus. ESI mass spectrometry of vinblastine and vincristine lead to significant mass spectra providing not only information on the molecular weight of the two alkaloids but also characteristic fragmentation patterns which will result useful when the identification of these alkaloids is required and will improve the specificity of analytical methods such as those based on HPLC quantifications of antitumor alkaloids at low levels.
Lit; No&S., Bohler,J., Keller,E., Frahm,A.W.: - Poster at 1.Burop.Gmd.Stud.Meeting: Pharmazie 53(3),29(1998) - J.Pharm.Biomed.AnaJ. 1998 (in press)
178
180
DETERMINATION OF MYCOPHENOLIC ACID IN HUMAN PLASMA BY HPLC
TOXICOLOGICAL ANALYSIS OF ALUMINUM IN DRINKING WATERS AND DIALYSIS SOLUTIONS
Pawinski T., Paruszewski R. Department of Drug Chemistry, Medical Academy, 1 Banacha Str., 02097 Warsaw, Poland. Mvcoohenolic acid IMPAI is the active metabolite of the immunosuppressive drug mycophenolate mofetil. We report a rapid HPLC - UV method for the determination of MPA in plasma. Plasma samples 0,5 ml with oxazepam added as internal standard /IS/ were extracted by BakerBond Cl8 solid phase extraction. 0,05 ml is injected into the Nova-Pak Cl8 column. Mobile phase consisted of 45% acetonitrilel 55% phosphoric acid I O,Oti%, v/v I at a flow rate 0.8 mllmin. Absorbance is measured at 254 nm. The retention times of MPA and IS were 3,6 and 25 min respectiily. The limit of detection was 0.5 mg/L. Recovery over the linear concentration range 0,5-20,O mg/l_ was about 90% with the CV 7,0%. Accuracy at 0,5 mg/L and 20 mg/L were 94% and 97% respecttvely. This method can be applied for therapeutic drug monitoring of mycophenolic acid in plasma.
M.A. Raqqi’, R. Mandrioli’, C. Sabbioni’, F. Bugamelli’ and G. Cantelli Forti” ??Department of Pharmaceutical Sciences, Via Belmeloro, 6, 40126 Bologna, Italy; * Department of Pharmacology, Via Imerio, 46, 40126 Bologna, Italy. Aluminum at trace levels (ppb) is a common contaminant of hemodialysis solutions; it can be responsible for severe illnesses in patients suffering from chronic renal failure who need long-term hemodialysis treatments. Chronic aluminum toxicity manifests itself with anemia, bone diseases, encephalopathiir and a neurological illness known as “dialysis dementia”. Aluminum toxicity originates from its accumulation in the bone and in the CNS; for this reason, Al has been recently associated to Alzheimer’s disease. Epidemiologiccll studies found a correlation between Mgh levels of Al in drinking waters and an high incidence of Alzheimer’s syndrome in the population. The need for a reliable method for Al determination in drinking waters and in dialysis solutions is thus apparent. The accurate and sensitive rpectrofluorimetric procedure developed employs Mordant Red 19 as a complexing reagent. After thermostatting at 70°C for 60 minutes, the emission of the fluorescent metal chelate was measured at 558 nm, exdting at 478 nm. The method shows a good linearity over the 1.0 - 80 ppb range. The limit of quantkatbn (LOQ) was 1.0 ppb, while the limit of detectton (LOD) was 0.5 ppb. It was found that an extractive step with an organic solvent gives hiiher sensittvity to the method, which proved to be suitable for the determination of aluminum in commercial dialysis fluids and in mineral waters.