RESUMEN
BACKGROUND: Paclitaxel (PCT) is a chemotherapeutic drug widely used for the treatment of several types of tumors, and its use is associated with severe adverse events, mainly neurologic and hematopoietic toxicities. The relation between systemic exposure and clinical response to PCT was previously described, making paclitaxel a potential candidate for therapeutic drug monitoring (TDM). The use of dried blood spot (DBS) sampling could allow complex sampling schedules required for TDM of PCT. The aim of this study was to develop and validate an LC-MS/MS assay for the quantification of PCT in DBS. METHODS: PCT was extracted from one 8â¯mm DBS punch with a mixture of methanol and acetonitrile, followed by chromatographic separation in a Kinetex C18 (50â¯×â¯4.6â¯mm, 2.6⯵m) column. Detection was performed in a 5500-QTRAP® mass spectrometer, with a run time of 2.3â¯min. RESULTS: The assay was linear in the range of 2.5 to 400â¯ngâ¯mL-1. Precision (CV%) and accuracy at the concentration levels of 7.5, 40 and 150â¯ngâ¯mL-1 were 1.69-4.9% and 106.25 to 109.92%, respectively. PCT was stable for 21â¯days at 25 and 45⯰C. The method was applied to DBS samples obtained from 34 patients under PCT chemotherapy. The use of a simple correction factor, derived from the correlation between PCT concentrations in plasma and DBS in this set of patients, allowed unbiased estimation of PCT plasma concentrations from DBS measurements, with similar clinical decisions using either plasma or DBS measurements. CONCLUSIONS: DBS testing of PCT concentrations represents a promising alternative for the dissemination of PCT dose individualization.
Asunto(s)
Pruebas con Sangre Seca , Monitoreo de Drogas , Paclitaxel/análisis , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Pruebas con Sangre Seca/instrumentación , Pruebas con Sangre Seca/métodos , Monitoreo de Drogas/instrumentación , Monitoreo de Drogas/métodos , Femenino , Humanos , Masculino , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem/instrumentación , Espectrometría de Masas en Tándem/métodosRESUMEN
Allele frequencies for 15 short tandem repeat (STR) loci were obtained from a sample of 110 individuals from the Calchaqui Valleys population (North-Western Argentina). The combined power of exclusion and combined power of discriminating for the 15 tested STR loci were 0.999964 and 0.9999999999999998, respectively. Matching probability was 1 in 4.58 × 10(15). Therefore, it may be concluded that the set of 15 STRs included in the AmpF STR Identifiler kit, represents a powerful tool for forensic applications, paternity testing and population genetics studies in the Calchaqui Valleys population.
Asunto(s)
Frecuencia de los Genes , Genética de Población , Repeticiones de Microsatélite , Argentina , Humanos , Reacción en Cadena de la PolimerasaRESUMEN
Frequency data of the short tandem repeat (STR) loci D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, HUMTH01, D4S243, D18S535, HUMF13A1 and D12S391 were determined in the Puna population (Andean region from north western Argentina). In this study, 5 out of the 14 loci did not meet Hardy-Weinberg expectations. The excess of homozygotes observed in most of the markers could be due to a Wahlund effect and/or inbreeding. The frequencies were significantly different from those of other compared populations from Europe and America. Forensic parameters indicated that the 14 loci studied in the Puna region are highly discriminating, but the lack of Hardy-Weinberg equilibrium in some of the markers must be taken into account in the application of these results to paternity and forensic casework.