Degradation of cyclophosphamide and 5-fluorouracil by UV and simulated sunlight treatments: Assessment of the enhancement of the biodegradability and toxicity.

The presence of pharmaceuticals in the environment has triggered concern among the general population and received considerable attention from the scientific community in recent years. However, only a few publications have focused on anticancer drugs, a class of pharmaceuticals that can exhibit cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic effects. The present study investigated the photodegradation, biodegradation, bacterial toxicity, mutagenicity and genotoxicity of cyclophosphamide (CP) and 5-fluorouracil (5-FU). The photodegradation experiments were performed at a neutral to slight pH range (7-7.8) using two different lamps (medium-pressure mercury lamp and a xenon lamp). The primary elimination of the parent compounds was monitored by means of liquid chromatography tandem mass spectrometry (LC-IT-MS/MS). NPOC (non-purgeable organic carbon) analyses were carried out in order to assess mineralization rates. The Closed Bottle Test (CBT) was used to assess ready biodegradability. A new method using Vibrio fischeri was adopted to evaluate toxicity. CP was not degraded by any lamp, whereas 5-FU was completely eliminated by irradiation with the mercury lamp but only partially by the Xe lamp. No mineralization was observed for the experiments performed with the Xe lamp, and a NPOC removal of only 18% was registered for 5-FU after 256 min using the UV lamp. Not one of the parent compounds was readily biodegradable in the CBT. Photo transformation products (PTPs) resulting from photolysis were neither better biodegradable nor less toxic than the parent compound 5-FU. In contrast, the results of the tests carried out with the UV lamp indicated that more biodegradable and non-toxic PTPs of 5-FU were generated. Three PTPs were formed during the photodegradation experiments and were identified. The results of the in silico QSAR predictions showed positive mutagenic and genotoxic alerts for 5-FU, whereas only one of the formed PTPs presented positive alerts for the genotoxicity endpoint.

TiO2 photocatalytic degradation and transformation of oxazaphosphorine drugs in an aqueous environment.

This study investigated the TiO2 photocatalytic degradation and transformation of the oxazaphosphorines ifosfamide (IFO), cyclophosphamide (CP) and trofosfamide (TRO). Under the optimum conditions of TiO2=100mg/L, IFO=100µg/L and solution pH=5.5, IFO was completely removed within 10min (k=0.433min(-1)). The results indicated that OHfree radicals generated by valence holes in the bulk solution were the predominant species for the degradation of IFO. At higher initial concentrations of oxazaphosphorines (20mg/L), >50% of TOC remained after 6h of reaction time, indicating that parent compounds were transformed to byproducts, which exhibit higher Microtox acute toxicities; chlorinated byproducts were likely the source of toxicity. Photocatalytic degradation pathways of the three oxazaphosphorines were proposed. IFO, CP and TRO follow very similar pathways and bond-breaking processes: ketonization and breaking of the CCl bond, the PN bond and the CN bond (N-dechloroethylation). Chloride (Cl(-)) release is likely the first and primary step in the decomposition process. Several of the identified byproducts were also metabolites, which implies that photocatalytic oxidation proceeds through pathways that are similar to metabolic pathways.

Cistitis crónica fibrótica telangectásica por ciclofosfamida / Fibrous chronic cystitis telangectasia for ciclofosfamide

Enfoque de estudio y manejo de pacientes pediátricos hematúricos, con antecedente de tratamiento previo con ciclofosfamida.Paciente femenino de 8 años, con antecedente de linfoma no Hodgkin diagnosticado a los 4 años, que es tratado durante un año en centro extranjero con quimioterapia que incluía ciclofosfamida, sin registro de protección vesical. Presenta también un síndrome atáxico de etiología desconocida. Tres años después consulta por disuria, hematuria recurrente micro y macroscópica con coágulos, presentando función renal normal. Estudio por imágenes (ecografía, pielografía y TAC), muestra imagen de defecto de llene de 4 cm a nivel del trígono vesical, sugerente de coágulo. Se descartan malformaciones vasculares y tumorales.Cistoscopía demostró una cistitis hemorrágica con telangectasias. Histología mostró cistitis crónicahemorrágica fibrosa G° III.Pacientes sometidos a terapias con ciclofosfamida o sus derivados deben recibir protección vesical con Ledoxina, para reducir al máximo este tipo de complicación. Este paciente es candidato a reemplazo vesical total, aún no operado por encontrarse en su centro de origen en el extranjero. Se discute la indicación quirúrgica y la técnica quirúrgica en este caso particular.