Monitoring of total antimony and its species by ICP-MS and on-line ion chromatography in biological samples from patients treated for leishmaniasis.
Results from a study are reported in which patients with leishmaniasis were monitored by whole blood, blood plasma, urine, and hair analysis, before, during, and after intramuscular administration of N-methyl meglumine antimoniate. Quadrupole ICP-MS was used for the detection of antimony and on-line ion chromatography for the separation of its species. After typically 30 consecutive daily injections of 5 mg antimony per kg of body weight, Sb concentrations of up to 250 microg L(-1) in whole blood and plasma, and 60 mg of Sb per gram of creatinine in urine, were measured 24 h after drug administration. Antimony in hair samples of these patients showed concentrations of up to 24 microg g(-1). Speciation studies of Sb5+ and Sb3+ in drug, urine, and plasma samples were performed by ion chromatography using a Hamilton PRP-100X anion exchange column and EDTA (2 or 20 mM, pH 4.7) as the mobile phases. Repeatability of elution time and peak area measurements for a 0.125 ng spike were <1.2% and <3.5%, respectively. Method detection limits for both species, using a 1:10 diluted urine or plasma sample, were typically 1.6 microg L(-1). The procedure was capable of separating the very intense drug peak from its inorganic species, thus permitting the first studies on the bio-transformation of N-methyl meglumine antimoniate to Sb5+ and Sb3+ in the human body.
Miekeley
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Department of Chemistry, Pontifical Catholic University (PUC-Rio), Rio de Janeiro, Brazil. miekeley@rdc.puc-rio.br
Mortari
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SR
Schubach
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AO
D000328:Adult; D000965:Antimony / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002852:Chromatography, Ion Exchange; D008401:Gas Chromatography-Mass Spectrometry; D006197:Hair / Q000737:chemistry; D006801:Humans; D007896:Leishmaniasis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077485:Meglumine Antimoniate; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony