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BACKGROUND: Many guidelines and safety measures led to a decrease in exposure to antineoplastic agents. Since healthcare workers are often exposed to lower concentrations than patients, a sensitive method is needed to quantify occupational exposure. OBJECTIVE: The aim of this study was to develop and validate a sensitive method for simultaneous detection and quantification of cyclophosphamide, ifosfamide and paclitaxel in urine by use of UPLC-MS/MS with a UniSpray ionisation source. METHODS: Compounds were extracted from urine using Novum simplified liquid extraction cartridges, separated on a C18 column, ionised by a UniSpray ionisation source and detected with MS/MS. In the second part of the study, a field study was performed to assess occupational exposure to antineoplastic agents. RESULTS: Eighty-three samples from healthcare workers were analysed and resulted in seventeen samples containing quantifiable concentrations of at least one compound. In conclusion, a sensitive method for simultaneous detection and quantification of cyclophosphamide (LLOQ 0.05 ng/mL), ifosfamide (LLOQ 0.3 ng/mL) and paclitaxel (LLOQ 0.7 ng/mL) was developed and validated. ispartof: JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES vol:1205 ispartof: location:Netherlands status: published

A temperature-controlled “ON/OFF” switchable electrochemical sensor was fabricated based on an adaptable conductive microgel film consisting of thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) and conductive poly(3,4-ethylenedioxythiophene) (PEDOT). The constructed sensor revealed good thermo-sensitivity and reversible switchability in 5-Fluorouracil (5-FU) detection. Cyclic voltammetry (CV) of 5-FU at the PNIPAM-PEDOT modified glassy carbon electrode (PNIPAM-PEDOT/GCE) displayed higher oxidation peak current (22.49 μA) when the solution temperature is raised above the lower critical solution temperature (LCST) of PNIPAM represent the “ON” state (40 ℃). This oxidation peak current (15.12 μA) obviously suppressed at below LCST (25 ℃) representing “OFF” state. The repeatable “ON/OFF” switching of the CV responses of 5-FU on the PNIPAM-PEDOT/GCE was achieved via controlling the solution temperature. In addition, this reversibly switched sensor lets determining 5-FU in a good sensitivity with a low detection limit of 15 nM at 40 ℃ compared to 25 ℃ (0.37 μM). This reversible switched electrochemical sensor provided a new idea for the application of thermo-responsive polymers.

We review the literature on the analysis of pharmaceutically-derived cytostatic compounds in the environment. Cytostatics are a major class of chemotherapy drugs used extensively in the fight against cancer. They are a broad group of mostly organic compounds possessing a diverse range of physico-chemical parameters. Their differences and their presence in the environment in trace amounts make their determination in complex matrices a major challenge. Despite the good scientific foundations laid by those in the field, it is apparent that past research has focused mainly on hospital effluents and few have analyzed environmental samples. Importantly, no study has looked at environmental transformation products that, along with human metabolites, could contribute to overall toxicity. To improve understanding of the chemodynamics of cytostatics in natural waters, it is essential to have more data on the occurrence and the fate of these compounds, including their human metabolites and environmental transformation products. This approach will require advanced sampling techniques and state-of-the-art analytical tools, including the latest separation methods and cutting-edge instrumentation.

Cisplatin is used frequently as an antineoplastic drug in the treatment of many different cancers. However, when used in doses over 360mg/m², ototoxicity may ensue, resulting in loss of hearing. Criteria for identifying and quantifying hearing loss have been devised. AIM: To describe the features of different hearing loss classification systems and to identify their implications and use in oncologic patients. METHOD: Hearing loss was classified in 31 patients before and after chemotherapy, according to different criteria, assessing the sensitivity and specificity of each classification system. RESULTS: Hearing loss results were highly variable (ranging from 29% to 61%). Only 4 of 31 subjects with post-therapy hearing loss were identified by all the methods. A few subjects with hearing loss were classified as normal hearing in some of the criteria. A normal PTA was found in 18 of 31 subjects in the post-treatment evaluation. CONCLUSION: None of the criteria assesses the complaints of patients. The criteria described in this study were inadequate to identify hearing loss following chemotherapy, requiring additional information for physicians to better understand the hearing losses and their implications for the quality of life of patients. A cisplatina é um antineoplásico muito utilizado no tratamento de diferentes neoplasias, porém quando utilizada em doses acima de 360mg/m² pode causar ototoxicidade. Esta produz lesões cocleares que resultam em perda auditiva. Existem critérios que visam identificar e quantificar as perdas auditivas. OBJETIVO: Descrever as características das classificações e identificar implicações e aplicações de cada uma, dentro das necessidades do acompanhamento ao paciente oncológico. MATERIAL E MÉTODO: Avaliamos 31 pacientes pré e pós-tratamento quimioterápico. Classificamos as perdas auditivas de acordo com os critérios e verificamos a sensibilidade e especificidade de cada um. RESULTADO: Houve grande variabilidade na detecção das alterações auditivas (de 29% a 61%). Somente 4 dos 31 indivíduos com alterações auditivas no exame pós-tratamento foram identificados por todos os critérios. Por vezes o indivíduo portador de perda auditiva era classificado com normal por algum critério. Dos 31 indivíduos, 18 apresentaram PTA normal no exame pós-tratamento. CONCLUSÃO: Nenhum dos critérios considera a queixa do paciente. Os critérios descritos mostraram inadequações para descrever as alterações auditivas encontradas, fazendo-se necessária a descrição de informações adicionais, para que o médico compreendesse a natureza da perda auditiva. É importante o refinamento desses instrumentos para melhor compreensão e tratamento dos pacientes oncológicos, assim como de sua qualidade de vida.

Hydroxyurea (HU) is an antineoplastic drug widely used in the clinical management of patients with sickle cell disease (SCD), and many questions related with its use remain unresolved. Given the severity of SCD, HU benefits, although not thoroughly confirmed, seem to outweigh its potential carcinogenicity. This study aimed to assess the genotoxicity associated with HU dose and treatment length by evaluating mutagenicity in patients with SCD treated with HU (SCHU) using the cytokinesis-block micronucleus assay (CBMN) in white cells. The study was conducted with 35 individuals in the SCHU group and 34 controls matched according to age, sex and smoking habit. CBMN results showed an increase (p=0.032) in the number of micronuclei (MN), but not of nucleoplasmic bridges (NPB) or nuclear buds (NBUD) in the SCHU group. The increased frequency of MN in the SCHU group was significantly correlated with treatment length and final HU dose, which confirms that patients with SCD treated with HU should be carefully monitored to reduce the risk of carcinogenicity.

The kinetics of an antineoplastic drug, suramin, described by a three-compartment, open, linear model is studied in this report. A population pharmacokinetic model, describing the pharmacokinetics of suramin, was developed using the iterative-two stage approach, with maximum a posteriori-Bayesian priors. It was further validated using data from a subsequent study (validation data set). The population pharmacokinetic parameters were also estimated by generating bootstrap samples from the validation data set. When the prior distribution was close to the population distribution, there was no significant difference between the estimates obtained using the iterative-two stage approach and the bootstrap approach. However, when estimating population pharmacokinetic parameters, the iterative-two stage approach was less sensitive to prior distribution specification

The antineoplastic drug etoposide has been prepared by a chemically and operationally simple process. The salient reaction is the BF3 etherate promoted, room temperature condensation of 4′-demethyl-4′-acetyl-epipodophyllotoxin 4, with α-1-Bu3Sn-O-2,3-bisacetyl-4,6-ethylidene-glucose 6. The latter compound was prepared from 4,6-β-ethylidene glucose triacetate and Bu3Sn-OMe obtained in situ from (Bu3Sn)2O and dimethyl carbonate. A readily separable mixture of α and β-etoposide triacetate epimers was obtained where the desired β-epimer predominated. In contrast, 4,6-α-ethylidene glucose diacetate and 4, even at 0°C, gave an equimolar mixture of epimers. It is proposed that the stereochemical outcome may be attributed to electronic effects in the activated tin-glucose reagent.

The chemical and pharmaceutical industry is under an accelerating pressure to find environmentally friendly organic reaction methodologies. Owing to the unique advantages of ionic liquids, the preparation and industrial applications of ionic liquids have attracted considerable interest. Herein we report novel synthesis of imidazolium based Room-Temperature Ionic Liquid (RTIL) using cheaper reagents which have been used for the synthesis of Antiandrogenic and Antineoplastic drug Bicalutamide and its impurities reported in US pharmacopoeia.

The pharmaceutical development of tablets of a 1,8 naphtalimide with antineoplastic activity is carried out in two steps. The preformulation step includes the study of those characteristics of the drug with special importance for the successful development of the formulation step. In this way, the low moisture, the low porosity and the good flowability of the drug as raw material allow direct compression to be taken into account, together with wet granulation as methods of tablet manufacture. As a result of the formulation studies, one formulation of tablets obtained by direct compression and another one obtained by wet granulation are selected. Both of them meet all the requirements imposed to a solid pharmaceutical form for oral administration.

Sorption by i.v. delivery systems and stability in different infusion fluid containers were investigated for bleomycin, epidoxorubicin and mmustine. Two infusion fluids were used: 0.9% NaCI and 5% glucose. A solution of 15 μg ml −1 bleomycin can be stored at room temperature, unprotected from daylight, for up to 24 h after reconstitution. Solutions of 50 μg ml −1 epidoxorubicin or 2 mg ml −1 nimustine kept at 4°C, protected from daylight, are stable for at least 25 and 6 days, respectively. During the stability testing no influence of the infusion fluid or packaging materials was observed. Dynamic experiments showed no sorption of any of the tested drugs by the infusion bags or administration sets. The use of end-line filters caused an initial, clinically unimportant loss of bleomycin and epidoxorubicin.

The antineoplastic drug doxorubicin is capable of generating a variety of free radical species in subcellular systems and this capacity has been considered critical for its antitumor action. However, for most tumor cell lines this mechanism of cytotoxicity does not appear to play a major role. Free radical-independent cytotoxicity mechanisms, taking place in the nuclear compartment of the cell, may more likely be involved in the antitumor effect of doxorubicin.

1. Digestive oncology – a changing fieldDigestive cancer accounts for a quarter of all cancers and con-siderable knowledge of the particular features of these disordersis required for correct treatment. Digestive oncology (DO) is amajor field of activity for hepato-gastroenterologists (HGE), whoare involved at all stages, from screening to diagnosis, follow-up,tumour evaluationandpalliativetreatment.HGEhavealsorecentlybeen recruited to multidisciplinary teams, due to their consider-able competence in the management of digestive cancers. OverallDO accounts for more than 50% of all admissions to most gas-troenterology (GI) departments. In Belgium, France and Germany,HGE withspecific,recognizedcompetenceareallowedtoadminis-ter chemotherapy and targeted therapies. In these countries, suchcompetence isconsideredtobeattainedaftertwoyearsoftrainingwith an additional course and certification controlled by special-ists in oncology. HGE work in close collaboration with the otherspecialists responsible for managing digestive cancer, as part ofmultidisciplinary teams. Together, Belgium, France and Germanyaccount for 40% of the European population (about 200 millionEuropean citizens). The system works well in these countries andit is not clear why other European countries have not also electedto allow HGE to perform these functions after specific training.Chemotherapy and targeted therapies are no more complex toadminister than other drugs regularly prescribed by HGE, suchas immunosuppressants, antiviral treatments and anti-TNF treat-ments.The reasonsforthissituationmaybehistorical,demographicoreven political.1.1. Historical aspectsWhen 5FU (fluorouracil Roche lb), the first antineoplastic drug,was discovered 50 years ago, HGE expressed great scepticism con-cerning its utility. However, the situation changed in the 1990s

A few previous reports have suggested that megestrol acetate, a synthetic progestational agent frequently used as an antineoplastic drug, suppresses serum cortisol concentrations in humans. To explore this concept further, we prospectively performed several measurements of the pituitary-adrenal axis in patients receiving megestrol acetate (160 or 800 mg/day). The data from these evaluations demonstrate that megestrol acetate reversibly decreases serum cortisol concentrations in humans and that this effect seems to originate from a suppression of the pituitary-adrenal axis. Additional studies should be conducted to determine the implications of the low levels of serum cortisol.

This study was designed to examine the interaction of oxaliplatin with human serum albumin (HSA) under physiological conditions by using fluorescence, absorption, FT-IR and circular dichroism (CD) spectroscopic techniques in combination with molecular docking study. Spectroscopic analysis of the emission quenching at different temperatures has revealed that the quenching mechanism of oxaliplatin with HSA was static quenching mechanism. The value of 1.64 nm for the distance r between the donor (HSA) and acceptor (oxaliplatin) was derived from the fluorescence resonance energy transfer. From the CD and FT-IR results, it was apparent that the interaction of oxaliplatin with HSA caused a conformational change of the protein. Molecular docking study showed that oxaliplatin bind to residues located in subdomain IIA of HSA. The effect of metal ions and amino acids on the binding constant of HSA–oxaliplatin complex was also discussed.

A 22-month-old, 10 kg child ingested 32 mg of chlorambucil and developed irritability, myoclonic-like muscle jerks, an exaggerated startle reflex, vomiting, and EEG changes within a few hours. The neurologic symptoms improved overnight, and the patient was discharged at about 28 hours postingestion. During the three weeks of follow-up, mild bone marrow suppression occurred and resolved. A normal EEG was reported at 33 weeks postingestion.

The ability to monitor biologically significant levels of antineoplastic drugs in patients' plasma is rapidly expanding. The expanded application of therapeutic drug monitoring to the clinical practice of oncology will require a better understanding of the relationship between drug levels, toxicity, and therapeutic benefit in particular patient populations.

The extended physical and chemical stability of 5-fluorouracil and methotrexate in 0.9% sodium chloride injection in PVC containers was monitored for periods of up to 3 months and compared to solutions stored in glass containers. For 5-fluorouracil, 50 mg/ml solutions stored at room temperature are stable for up to 42 days and 5 mg/ml solutions for up to 13 weeks of refrigerated storage (5 ± 3°C) plus an additional week at room temperature. Methotrexate solutions at concentrations ranging from 1.25 to 12.5 mg/ml are stable for up to 15 weeks of refrigerated storage followed by an additional week at room temperature. No physical or chemical modifications of the solutions were observed, the only limiting factor for long-term stability being a progressive increase in drug concentration due to evaporative water loss from the PVC containers. Except for this slight increase in drug concentration, the same results were obtained for both plastic and glass containers.

The use of parenteral fat emulsions for development of an extemporaneous preparation of an intravenous formulation of a poorly water-soluble and unstable investigational anticancer agent (NSC no. 278214) is presented. The incorporation into a commercial fat emulsion of the drug, dissolved in dimethylacetamide-cremophor solution, results in a suitable parenteral formulation in which the drug is approximately 100-fold more stable than in simple aqueous solutions.

A simple and unitary model for simultaneous evaluation of antineoplastic and immunodepressive actions of drugs is proposed. C57 BL/6 male mice bearing syngeneic grafts of methylcholanthrene induced sarcoma (first-third transplant generation), were treated with an antineoplastic drug;tumours were excised on the 10th day. Animals received a second tumour transplantation 22 days after the first one. Antineoplastic effect was evaluated from the reduced development of the first transplanted tumour. Immunodepressive effect from the favoured development of the second transplanted tumour.

The effect of a single dose of external X-radiation (range 250–2000 rads) and a single dose of cyclophosphamide (0·6 mg/100 g body weight) 2–6 days after its administration was studied for the uptake of 203 HgCl 2 by the transplantable Yoshida sarcoma in the rat. In order to evaluate the influence of the two forms of treatment, the size of the tumor was measured and histologic examinations were performed. After radiation there was a dose-dependent decrease of the tumor uptake of 203 HgCl 2 and after the antineoplastic drug a time-dependent decrease. In both instances the decline of the 203 HgCl 2 tumor uptake parallelled the increasing influence of the two forms of treatment on the tumor in relation to its growth and its histologic pattern.