A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours.

Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 µm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100-10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 µmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7-19.7 µmol/L. The median at 12 hours was 19.5 µmol/L (Q25 14.4-Q75 29.0) and 3.8 µmol/L (Q25 1.5-Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients.

Motivos de hospitalización en pacientes con tuberculosis pulmonar en un hospital de referencia / Reasons for medical admission in patients with pulmonary tuberculosis in a referral institute

Objetivo: Determinar la prevaíencia de complicaciones torácicas en pacientes con tuberculosis pulmonar hospitalizados en el Instituto Nacional de Enfermedades Respiratorias (INER). Lugar del estudio: INER, centro de tercer nivel y referencia dedicado a la atención médica especializada, docencia e investigación de enfermedades respiratorias. Material y métodos: Se realizó un estudio retrospectivo con la revisión de los expedientes clínicos de pacientes con tuberculosis pulmonar ingresados al INER, en un período que comprendió del 1 de julio al 31 de diciembre de 2003. Resultados: De los 124 pacientes con tuberculosis pulmonar que acudieron al INER durante el período de estudio, 62.9% (78/124) fueron hospitalizados; 44.9% (35/78) del sexo masculino; mediana de edad, 44.5 años (rango 16-78); el diagnóstico bacteriológico se hizo por baciloscopía en 51.3% (40/78); sólo por cultivo, 5.1% (4/78) y por baciloscopía y cultivo, 43.6% (34/78). Del total de pacientes, 66.6% (52/78) se clasificaron en la categoría I de la Organización Mundial de la Salud. La prevaíencia de diabetes mellitus fue 43.7% (31/78). Los motivos de hospitalización fueron: 46.2% (36/78) para diagnóstico; hemoptisis, 34.6% (27/78); infecciones, 5.2% (4/78) y otros motivos, 14.0% (11/78). Presentaron bronquiectasias, 85.7% (66/78); neumonía, 6.4% (5/78); neumonía por Mycobacterium tuberculosis, 5.1% (4/78); empierna, 5.1% (4/78); fístula broncopleural, 3.9% (3/78); aspergiloma, 2.6% (2/78); compresión tráqueo-bronquial, 1.3% (l/78) y fibrotórax, 12.8% (10/78). Conclusiones: Los pacientes hospitalizados en el INER por tuberculosis pulmonar manifestaron una elevada frecuencia de complicaciones, especialmente de bronquiectasias y hemoptisis. Casi 44% de los pacientes presentó diabetes mellitus; uno de cada dos fue hospitalizado para diagnóstico.

Purpose: To determine the prevalence of thoracic complications in hospitalized patients with pulmonary tuberculosis. Setting: National referral hospital for the care, teaching and investigation of respiratory diseases. Material and methods: This study is based on the retrospective analysis of pulmonary tuberculosis patients admitted from July 1 to December 31, 2003 and was conducted at The National Institute of Respiratory Diseases (INER), Mexico. Results: Seventy eight patients with pulmonary tuberculosis were included in the six month period; 35 (44.9%) were male; the bacteriological diagnosis was done by sputum smear in 51.3% (40/78), culture in 5.1% (4/78) and sputum smear and culture in 43.6% (34/78). Patients were classified as WHO category I in 66.7% (52/78); 43.7% had diabetes mellitus (31/78). Admission causes: for diagnosis in 46.2% (36/78); hemoptysis in 34.6% (27/78); infection in 5.2% (4/78); other causes in 14.0% (11/78); bronchiectasis were present in 85.7% (66/ 77); pneumonia in 6.4% (5/78); Mycobacterium tuberculosis pneumonia in 5.1% (4/78); empyema in 5.1% (4/78); bronchopleural fistula in 3.9% (3/ 78); aspergilloma in 2.6% (2/78); tracheobronchial obstruction in 1.3% (1/78); fibrothorax in 12.8% (10/78). Conclusions: Hospitalized pulmonary tuberculosis patients show an elevated rate of pulmonary complications. Almost half had diabetes mellitus; almost half were hospitalized for diagnosis.