Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
Anal Bioanal Chem ; 414(2): 1163-1176, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34718838

RESUMO

Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique capable of increasing the Raman signal of an analyte using specific nanostructures. The close contact between those nanostructures, usually a suspension of nanoparticles, and the molecule of interest produces an important exaltation of the intensity of the Raman signal. Even if the exaltation leads to an improvement of Raman spectroscopy sensitivity, the complexity of the SERS signal and the numbers of parameters to be controlled allow the use of SERS for detection rather than quantification. The aim of this study was to develop a robust discriminative and quantitative analysis in accordance with pharmaceutical standards. In this present work, we develop a discriminative and quantitative analysis based on the previous optimized parameters obtained by the design of experiments fixed for norepinephrine (NOR) and extended to epinephrine (EPI) which are two neurotransmitters with very similar structures. Studying the short evolution of the Raman signal intensity over time coupled with chemometric tools allowed the identification of outliers and their removal from the data set. The discriminant analysis showed an excellent separation of EPI and NOR. The comparative analysis of the data showed the superiority of the multivariate analysis after logarithmic transformation. The quantitative analysis allowed the development of robust quantification models from several gold nanoparticle batches with limits of quantification of 32 µg/mL for NOR and below 20 µg/mL for EPI even though no Raman signal is observable for such concentrations. This study improves SERS analysis over ultrasensitive detection for discrimination and quantification using a handheld Raman spectrometer.


Assuntos
Epinefrina/análise , Ouro/química , Nanopartículas Metálicas/química , Norepinefrina/análise , Análise Espectral Raman/métodos
2.
Eur J Cancer Care (Engl) ; 30(3): e13396, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33340189

RESUMO

OBJECTIVE: The development of oral chemotherapy (OC) has led to the recent establishment of multidisciplinary programmes involving pharmacists. We evaluated the utility of our local programme for detecting potential interactions with OCs, particularly drug-drug interactions (DDIs) and herbal-drug interactions (HDIs). METHODS: We performed a single-centre retrospective descriptive study of patients on OC attending a pharmaceutical consultation (PC) during a seven-month period. These consultations included the use of various complementary tools/databases to search for interactions. RESULTS: We analysed 308 treatments taken by 42 consecutive patients. Fifty-four potential interactions with OCs were detected in 26% (n = 79) of the treatments taken by patients: 46 DDIs (32 minor, 12 major, 2 contraindicated) and eight HDIs. Five interventions associated with interactions were suggested by pharmacists during the consultations (4 were taken into account by oncologists). The total mean time spent on each PC for an individual patient was 80 minutes (36 minutes of preparation, 44 minutes with the patient). CONCLUSION: This pilot study highlights the importance of studying interactions in such patients, and of the expertise of pharmacists for detecting interactions, which were found in more than one in four treatment lines. The further development of such activities, which already take up considerable amounts of time, is therefore warranted.


Assuntos
Interações Medicamentosas , Preparações Farmacêuticas , Farmacêuticos , Encaminhamento e Consulta , Estudos Transversais , Humanos , Projetos Piloto , Estudos Retrospectivos
3.
J Oncol Pharm Pract ; 25(5): 1195-1203, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30691354

RESUMO

PURPOSE: Cancer chemotherapy is a high-risk process. To improve patient safety, a systematic pharmaceutical analysis of chemotherapy prescriptions is performed in our institution. The aim of this study was to assess the impact of pharmaceutical interventions (PIs) on the safety of patient chemotherapy prescriptions. METHODS: This prospective cross-sectional study was conducted in an 800-bed university hospital with oncology departments. All chemotherapy prescriptions were included and PIs were collected prospectively during one month. The clinical impact of PIs was scored by an expert panel of oncologists and pharmacists, using the Hatoum scale. Univariate and multivariate analysis were conducted to identify factors associated with a higher frequency of PIs. RESULTS: Of 1346 prescriptions included, 129 required a PI (9.6% (95% CI: 8.1-11.4)). Most PIs were scored as having at least a significant impact for patient safety (69.8% (95% CI: 60.4-76.9)). The frequency of PIs was significantly associated with tumour site (p = 0.04) and weekday of prescription (p = 0.005). Multivariate analysis identified factors independently associated with PI performance, including pancreas and biliary tract cancers (odds ratio = 2.8 (95% CI: 1.4-5.3)), ovary cancers (odds ratio = 2.4 (95% CI: 1.2-4.8)) and head and neck cancers (odds ratio = 2.4 (95% CI: 1.1-5.1)) and the day 1 of the protocol with a cytotoxic agent (odds ratio = 3.7 (95% CI: 1.1-11.1)). CONCLUSIONS: Oncology pharmacists have a critical role in the safety of chemotherapy prescriptions. The coordination between healthcare professionals and access to patient data seem essential to improve the PIs' relevance and their clinical impact on patient safety.


Assuntos
Neoplasias/tratamento farmacológico , Segurança do Paciente , Farmacêuticos , Serviço de Farmácia Hospitalar , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papel Profissional , Estudos Prospectivos
4.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1862(10 Pt A): 1079-1091, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28739279

RESUMO

A diet containing a high n-3/n-6 polyunsaturated fatty acids (PUFA) ratio has cardioprotective properties. PUFAs incorporation into membranes influences the function of membrane proteins. We investigated the impact of the membrane incorporation of PUFAs, especially eicosapentaenoic acid (EPA) (C20:5 n-3), on the anti-atherogenic cholesterol efflux pathways. We used cholesteryl esters (CE)-loaded human monocyte-derived macrophages (HMDM) to mimic foam cells exposed to the FAs for a long period of time to ensure their incorporation into cellular membranes. Phospholipid fraction of EPA cells exhibited high levels of EPA and its elongation product docosapentaenoic acid (DPA) (C22:5 n-3), which was associated with a decreased level of arachidonic acid (AA) (C20:4 n-6). EPA 70µM reduced ABCA1-mediated cholesterol efflux to apolipoprotein (apo) AI by 30% without any alteration in ABCA1 expression. The other tested PUFAs, DPA, docosahexaenoic acid (DHA) (C22:6 n-3), and AA, were also able to reduce ABCA1 functionality while the monounsaturated oleic FA slightly decreased efflux and the saturated palmitic FA had no impact. Moreover, EPA also reduced cholesterol efflux to HDL mediated by the Cla-1 and ABCG1 pathways. EPA incorporation did not hinder efflux in free cholesterol-loaded HMDM and did not promote esterification of cholesterol. Conversely, EPA reduced the neutral hydrolysis of cytoplasmic CE by 24%. The reduced CE hydrolysis was likely attributed to the increase in cellular TG contents and/or the decrease in apo E secretion after EPA treatment. In conclusion, EPA membrane incorporation reduces cholesterol efflux in human foam cells by reducing the cholesteryl ester mobilization from lipid droplets.


Assuntos
Membrana Celular/metabolismo , Ésteres do Colesterol/metabolismo , Ácido Eicosapentaenoico , Gotículas Lipídicas/metabolismo , Macrófagos/metabolismo , Transportador 1 de Cassete de Ligação de ATP/biossíntese , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/biossíntese , Ácido Eicosapentaenoico/farmacocinética , Ácido Eicosapentaenoico/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lipoproteínas HDL/metabolismo , Masculino , Receptores Depuradores Classe B/biossíntese
7.
Pharm Res ; 32(5): 1794-803, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25504453

RESUMO

PURPOSE: Nanoparticles with prolonged residence time in bone constitute a valuable strategy for bone disease treatments. The aim of this work was to synthesise a simple nanoparticulate system exhibiting both anticancer and hydroxyapatite binding properties for potential bone cancer applications. METHODS: The amphiphilic copolymer poly(γ-benzyl-glutamate)-block-poly(glutamic acid) (PBLG-b-PGlu) was synthetised by ring opening polymerization and nanoparticles were obtained by a simple nanoprecipitation method. Nanoparticles were characterized in terms of cisplatin interaction, association, and release as well as interaction with hydroxyapatite and their cytoxicity was studied in three prostate cancer cell lines. RESULTS: PBLG-b-PGlu nanoparticles of ~50 nm in size were successfully prepared. They could display for the first time dual hydroxyapatite binding and anticancer properties mediated by the PGlu moiety. They could complex cisplatin at a drug loading content of 6.2% (w/w). Cisplatin release was triggered by physiological concentrations of chloride ions according to an almost zero order kinetics during 14 days. Simultaneously, these nanoparticles showed in vitro hydroxyapatite binding. Finally, they were shown to exert a cytotoxic effect in three prostate cancer cell lines that potentially metastasize to bone. CONCLUSIONS: These properties suggest the potential utility of cisplatin-loaded PBLG-b-PGlu nanoparticles as carrier systems for the treatment of bone metastases.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Preparações de Ação Retardada/química , Durapatita/química , Nanopartículas/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Humanos , Masculino , Ácido Poliglutâmico/química , Próstata/efeitos dos fármacos , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia
8.
J Pharm Biomed Anal ; 252: 116469, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39265204

RESUMO

A transmission detection mode was investigated with SERS analyses (SETRS). A comparison between backscattering and transmission detection modes was conducted to demonstrate the feasibility of performing SETRS analyses. The impact of various parameters on the SERS signal intensity such as sample volume, lens collection optic, laser beam size and laser power were then examined. The analytical performances of SETRS were further evaluated through the quantification of an impurity (4-aminophenol) ranging from 3 to 20 µg/mL in a commercial pharmaceutical product using a total error risk-based approach. To account for expected variability of routine analysis, 9 batches of silver nanoparticles suspensions were used and experiments were performed over 5 different days and by 2 operators. Univariate spectral analysis based on a quadratic regression was compared to a multivariate approach using a partial least square regression. The presented results demonstrated that SETRS can be used to determine an impurity in a complex matrix opening new perspectives for quantitative applications.

9.
Int Arch Occup Environ Health ; 86(3): 333-41, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22526087

RESUMO

PURPOSE: To minimize the risk of chronic occupational exposure of antineoplastic drugs, cleaning procedures must be evaluated. This study was conducted to compare the detergent efficiency of cleaning solutions (two hydro-alcoholic solutions, three disinfectants and two detergents) used in different cleaning protocols. METHODS: The central surface of a stainless steel plate (30 × 50 cm) was exposed to a carboplatin solution equivalent to 105,100 ng of platinum. After cleaning according to a standardized protocol, residual platinum contaminations were assayed on 10 × 10 cm sections. RESULTS: After standardized cleaning, the residual quantity of platinum on the surface of the deposit accounted for between 1.0 and >15 % of the initial deposit. Spread of contamination on the plate depended on the cleaning movement and was between 2.1 and 53.9 % of the total quantity on the plate. The two detergents were more efficient (2,793-4,780 ng/plate) than hydro-alcoholic solutions (>20,000 ng/plate). The efficacy of the disinfectant was intermediate (5,891-6,122 ng/plate for solutions and 15,360 ng/plate for pre-soaked gauze). The cleaning protocol was also important with better efficiency of 8 mL of cleaning solution for 1,500 cm(2) (versus 4 mL), sprayed directly on the plate (versus wiping) with no contact time (versus 5 min). CONCLUSION: The efficacy of chemical decontamination of cytotoxic work surfaces depends not only on the cleaning solution used, but also on the cleaning protocol. It is necessary to adapt the protocol to the surface to clean and it must be standardized and validated. This work is an example of an experimental procedure to evaluate the efficacy of cleaning solutions and protocols used at a workstation after exposure to antineoplastic drugs.


Assuntos
Antineoplásicos , Descontaminação/métodos , Detergentes/uso terapêutico , Desinfetantes/uso terapêutico , Local de Trabalho , Contaminação de Equipamentos , Humanos , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Saúde Ocupacional
10.
Talanta ; 251: 123752, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35926414

RESUMO

Surface enhanced Raman scattering (SERS) has become widely used for identification, quantification and providing structural information about molecular structure in low concentrations as it allows signal Raman enhancement using metallic nanoparticles (NPs). Controlling interaction between analyte and NPs is a major point for the optimization of signal exaltation in SERS analysis. The objective of this study is the improvement and the control of SERS analysis by aggregation/self-assembly optimization of AuNPs using quaternized chitosan. The interest of this approach is to allow stable and reliable measurements with a simple and low cost approach compatible with a massive use in the field. In this work, we used design of experiments by Box-Behnken design to fix optimized conditions to increase signal sensibility of epinephrine water solutions. We also tested SERS signal stability in isotonic sodium chloride 0.9% and glucose 5% matrices. Our results demonstrate that globally neutral AuNPs aggregates were stabilized at a nanometric size by the subsequent addition of polyelectrolyte chains and allows for significant Raman signal enhancement of epinephrine. We succeed to prepare the SERS active material and measure a stable signal of epinephrine at a concentration as down as 0.1 µg mL-1 in less than 5 min. The signal remained stable and exploitable for at least 2 h. Our results reveal a strong correlation between intensity and logarithm of the concentration (concentration before dilution from 0.1 to 10 µg mL-1) suggesting a possible quantification. Furthermore, the signal of epinephrine at 10 µg mL-1 were also exploitable and stable in complex media as isotonic sodium chloride 0.9% and glucose 5%. This represents a particularly interesting application that would allow direct analysis of drugs complex media and open the way to analysis in biological samples.


Assuntos
Quitosana , Nanopartículas Metálicas , Epinefrina , Glucose , Ouro/química , Nanopartículas Metálicas/química , Polieletrólitos , Cloreto de Sódio , Análise Espectral Raman/métodos , Água
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 268: 120628, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-34810096

RESUMO

Surface Enhanced Raman Scattering (SERS) spectroscopy is a rapid and innovative analysis technique involving metallic nanoparticles (NPs). The interaction between NPs and norepinephrine gives an exaltation of the Raman signal under certain experimental conditions. The control of the signal exaltation, crucial for sensitive analyses, remains one of the main limitations of this technique. The aim of this work is to optimize the exaltation conditions for an optimal SERS signal at two concentrations of norepinephrine (NOR) and spherical gold NPs in suspension. This first work will fix the optimal experimental conditions essential for the development of robust discriminant and quantitative analysis of catecholamine. Two complete 3-factors 3-levels experiment designs were performed at 20 µg.mL-1 and 100 µg.mL-1 norepinephrine concentrations, each experiment being repeated 3 times. The optimization factors were the process of synthesis (variation of the quantity of gold and citrate used for the three synthesis SA, SB and SC) and HCl (0.3 M, 0.5 M, 0.7 M) as well as the volume ratio of NPs and norepinephrine (0.5, 2, 3.5) for SERS acquisition. Spectral acquisitions were performed with a handheld Raman spectrometer with an excitation source at 785 nm. For each sample, 31 acquisitions were realized during 3 s every 8 s. The optimization parameter was the intensity of the characteristic band of norepinephrine at 1280 cm-1. A total of 5,042 spectra were acquired and the pre-treatment selected for all spectra was asymmetric least square combined to a smoothing of Savistsky Golay (ALS - SG). The optimal contact time between norepinephrine and NPs depends on the experimental conditions and was determined for each experiment according to the mean intensity between the three replicates. After interpretation of the experimental designs, the optimal conditions retained were the quantity of gold corresponding to SA and the HCl concentration 0.7 M for the two concentrations of norepinephrine. Indeed, the optimal volume ratio depend on the NOR concentration.


Assuntos
Ouro , Nanopartículas Metálicas , Análise Espectral Raman , Suspensões
12.
Clin Res Hepatol Gastroenterol ; 45(4): 101474, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32917564

RESUMO

This case report relates to the first-in-man use of a vessel occluder gel medical device as a fistula occluder in a repurposing strategy. A patient with chronic colocutaneous fistula received an off-label treatment with a thermoresponsive Poloxamer 407 gel (20%) via percutaneous administration and injected under endoscopic control. Treatment consisted in the association of esophageal stent placement and gel injection. The product was administered just after the stent placement at<20°C in its liquid form, gelling at body temperature to form a fistula plug. However, the stent was removed at day 26 because of major pain and the fistula was still present. Treatment was continued a total of 14 administrations of thermoresponsive Poloxamer 407 gel during 7 weeks via the external fistula orifice. The treatment reduced fistula orifice diameter from 4.0±0.5 to 1mm and fistula daily output decreased from 425±65 to 23±4mL, when comparing the months before and after treatment. Gel administration was not associated with any toxic effects. The therapeutic outcome remained stable 1 year after treatment. The external fistula diameter and the fistula output were similar to what was observed after the last Poloxamer 407 gel administration.


Assuntos
Fístula Cutânea , Uso Off-Label , Fístula Cutânea/terapia , Humanos , Poloxâmero , Polímeros , Stents
13.
Viruses ; 13(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466377

RESUMO

Bacteriophages are a promising therapeutic strategy among cystic fibrosis and lung-transplanted patients, considering the high frequency of colonization/infection caused by pandrug-resistant bacteria. However, little clinical data are available regarding the use of phages for infections with Achromobacter xylosoxidans. A 12-year-old lung-transplanted cystic fibrosis patient received two rounds of phage therapy because of persistent lung infection with pandrug-resistant A. xylosoxidans. Clinical tolerance was perfect, but initial bronchoalveolar lavage (BAL) still grew A. xylosoxidans. The patient's respiratory condition slowly improved and oxygen therapy was stopped. Low-grade airway colonization by A. xylosoxidans persisted for months before samples turned negative. No re-colonisation occurred more than two years after phage therapy was performed and imipenem treatment was stopped. Whole genome sequencing indicated that the eight A. xylosoxidans isolates, collected during phage therapy, belonged to four delineated strains, whereby one had a stop mutation in a gene for a phage receptor. The dynamics of lung colonisation were documented by means of strain-specific qPCRs on different BALs. We report the first case of phage therapy for A. xylosoxidans lung infection in a lung-transplanted patient. The dynamics of airway colonization was more complex than deduced from bacterial culture, involving phage susceptible as well as phage resistant strains.


Assuntos
Achromobacter denitrificans/efeitos dos fármacos , Fibrose Cística/microbiologia , Infecções por Bactérias Gram-Negativas/terapia , Terapia por Fagos , Pneumonia Bacteriana/terapia , Antibacterianos/farmacologia , Criança , Fibrose Cística/cirurgia , Farmacorresistência Bacteriana , Humanos , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Transplante de Pulmão/efeitos adversos , Masculino , Sequenciamento Completo do Genoma
14.
Molecules ; 15(1): 352-73, 2010 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-20110896

RESUMO

Phospholipids are essential constituents of all living cell membranes. There are many analytical methods available for the quantitative and qualitative determination of phospholipids, but since these molecules lack chromophores, common absorbance based methods are of limited use. Beside mass spectrometry, some less specific approaches that are routinely used are evaporative light scattering detection or fluorescence, which exhibit sufficient sensitivity. Here, we focus on fluorescence, which remains an interesting way to quantify phospholipids. Two ways of detecting phospholipids by fluorescence are possible coupled with separation techniques such as thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and capillary electrophoresis (CE): firstly, pre-column derivatization procedures and secondly, probe assisted post-column detection with suitable fluorescence reagents. In both cases, the common purpose is to increase the detection sensitivity. It is shown that, whereas pre-column derivatization is characterized by selectivity due to the chemical functionality of the analyte involved in the derivatization process, in supramolecular post-column derivatization, the selectivity only proceeds from the capacity of the lipid to involve supramolecular assemblies with a fluorescence probe. The aim of this review is to summarize available experiments concerning fluorescence detection of phospholipids. The interest and limitation of such detection approaches are discussed.


Assuntos
Corantes Fluorescentes/química , Fosfolipídeos/análise , Animais , Fosfolipídeos/química , Fosfolipídeos/isolamento & purificação
15.
Talanta ; 217: 121040, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32498908

RESUMO

Antineoplastic agents are, for most of them, highly toxic drugs prepared at hospital following individualized prescription. To protect patients and healthcare workers, it is important to develop analytical tools able to identify and quantify such drugs on a wide concentration range. In this context, surface enhanced Raman spectroscopy (SERS) has been tested as a specific and sensitive technique. Despite the standardization of the nanoparticle synthesis, a polydispersity of nanoparticles in the suspension and a lack of reproducibility persist. This study focuses on the development of a new mathematical approach to deal with this nanoparticle polydispersity and its consequences on SERS signal variability through the feasibility of 5-fluorouracil (5FU) quantification using silver nanoparticles (AgNPs) and a handled Raman spectrophotometer. Variability has been maximized by synthetizing six different batches of AgNPs for an average size of 24.9 nm determined by transmission electron microscopy, with residual standard deviation of 17.0%. Regarding low performances of the standard multivariate data processing, an alternative approach based on the nearest neighbors were developed to quantify 5FU. By this approach, the predictive performance of the 5FU concentration was significantly improved. The mean absolute relative error (MARE) decreased from 16.8% with the traditional approach based on PLS regression to 6.30% with the nearest neighbors approach (p-value < 0.001). This study highlights the importance of developing mathematics adapted to SERS analysis which could be a step to overcome the spectral variability in SERS and thus participate in the development of this technique as an analytical tool in quality control to quantify molecules with good performances, particularly in the pharmaceutical field.


Assuntos
Antineoplásicos/análise , Fluoruracila/análise , Nanopartículas Metálicas/química , Prata/química , Humanos , Análise dos Mínimos Quadrados , Dinâmica não Linear , Tamanho da Partícula , Análise Espectral Raman , Propriedades de Superfície
16.
J Pharm Sci ; 108(10): 3252-3261, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31201907

RESUMO

Compounded therapeutic mAbs used in a hospital require quality control (QC). In our hospital, analytical QC process intended to mAbs identification and quantification is based on flow injection analysis associated with second-derivative UV spectroscopy and matching method algorithm. We studied the influence of degraded mAbs after compounding on this validated QC. Three forced stress conditions including mechanical, thermal, and freeze-thawing stresses were studied to yield degraded mAbs from 2 model compounds, that is, bevacizumab (IgG1) and nivolumab (IgG4). Different degraded mAbs were generated and were analyzed in terms of turbidity, the percentage of aggregation, size distribution, and changes in tertiary structure. Stresses showed to be mAb-dependent in terms of aggregation. Tertiary structural changes were observed in most of the stressed samples by principal component analysis of the UV second-derivative data. The structural and physicochemical modifications conducted to mismatch depending on the nature of the stress. The mismatch ranged from 17% to 72% for the mAbs, except for freeze-thawed bevacizumab for which a perfect match (100%) was reached. The quantification with an unfulfilled relative error of the concentration (i.e., > ±15%) was detected only for mechanically stressed mAbs. In conclusion, the study revealed that the influence of the mAbs and the type of stress impact on the QC of compounded mAbs.


Assuntos
Anticorpos Monoclonais/química , Bevacizumab/química , Composição de Medicamentos/métodos , Congelamento , Hospitais , Nivolumabe/química , Controle de Qualidade
17.
Biomed Res Int ; 2018: 8746729, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065947

RESUMO

This study was conducted to evaluate the ability of Raman spectroscopy (RS) to control antineoplastic preparations used for chemotherapy in order to ensure its physical and chemical qualities. Three taxane drugs: cabazitaxel (CBX), docetaxel (DCX) and paclitaxel (PCX) at therapeutic concentration ranges were analyzed using a handheld spectrometer at 785 nm. Qualitative and quantitative models were developed and optimized using a calibration set (n=75 per drug) by partial least square discriminant analysis and regression and validated using a test set (n=27 per drug). All samples were correctly assigned with an accuracy of 100%. Despite optimization, quantitative analysis showed limited performances at the lowest concentrations. The root mean square error of predictions ranged from 0.012 mg/mL for CBX to 0.048 mg/mL for DCX with a minimal coefficient of determination of 0.9598. The linearity range was validated from 0.175 to 0.30 mg/mL for CBX, from 0.40 to 1.00 mg/mL for DCX and from 0.57 to 1.20 mg/mL for PCX. Despite some limitations, this study confirms the potential of RS to control these drugs and also provides substantial advantages to secure the activity for healthcare workers. As a result of its rapidity and the uncomplicated use of a handheld instrument, RS appears to be a promising method to augment security of the medication preparation process in hospitals.


Assuntos
Antineoplásicos/química , Análise Espectral Raman , Taxoides/química , Antineoplásicos/normas , Calibragem , Análise Discriminante , Humanos , Taxoides/normas
18.
Eur J Pharm Sci ; 111: 158-166, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28966101

RESUMO

The aim of this study was to assess the ability of Raman spectroscopy to discriminate and quantify five antineoplastic drugs in an aqueous matrix at low concentrations before patient administration. Five antineoplastic drugs were studied at therapeutic concentrations in aqueous 0.9% sodium chloride: 5-fluorouracil (5FU), gemcitabine (GEM), cyclophophamide (CYCLO), ifosfamide (IFOS) and doxorubicin (DOXO). All samples were packaged in glass vials and analyzed using Raman spectrometry from 400 to 4000cm-1. Discriminant analyses were performed using Partial Least Squares Discriminant Analysis (PLS-DA) and quantitative analyses using PLS regression. The best discrimination model was obtained using hierarchical PLS-DA models including three successive models for concentrations higher than the lower limit of quantification (0% of fitting and cross-validation error rate with an excellent accuracy of 100%). According to these hierarchical discriminative models, 90.8% (n=433) of external validation samples were correctly predicted, 2.5% (n=12) were misclassified and 6.7% (n=32) of the external validation set were not assigned. The quantitative analysis was characterized by the RMSEP that ranged from 0.23mg/mL for DOXO to 3.05mg/mL for 5FU. The determination coefficient (R2) was higher than 0.9994 for all drugs evaluated except for 5FU (R2=0.9986). This study provides additional information about the potential value of Raman spectroscopy for real-time quality control of cytotoxic drugs in hospitals. In some situations, this technique therefore constitutes a powerful alternative to usual methods with ultraviolet (UV) detection to ensure the correct drug and the correct dose in solutions before administration to patients and to limit exposure of healthcare workers during the analytical control process.


Assuntos
Antineoplásicos/análise , Modelos Teóricos , Análise Espectral Raman/métodos , Calibragem , Análise Discriminante , Limite de Detecção , Reprodutibilidade dos Testes , Soluções , Análise Espectral Raman/instrumentação , Fatores de Tempo
19.
Talanta ; 184: 260-265, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29674041

RESUMO

The use of monoclonal antibodies (mAbs) constitutes one of the most important strategies to treat patients suffering from cancers such as hematological malignancies and solid tumors. These antibodies are prescribed by the physician and prepared by hospital pharmacists. An analytical control enables the quality of the preparations to be ensured. The aim of this study was to explore the development of a rapid analytical method for quality control. The method used four mAbs (Infliximab, Bevacizumab, Rituximab and Ramucirumab) at various concentrations and was based on recording Raman data and coupling them to a traditional chemometric and machine learning approach for data analysis. Compared to conventional linear approach, prediction errors are reduced with a data-driven approach using statistical machine learning methods. In the latter, preprocessing and predictive models are jointly optimized. An additional original aspect of the work involved on submitting the problem to a collaborative data challenge platform called Rapid Analytics and Model Prototyping (RAMP). This allowed using solutions from about 300 data scientists in collaborative work. Using machine learning, the prediction of the four mAbs samples was considerably improved. The best predictive model showed a combined error of 2.4% versus 14.6% using linear approach. The concentration and classification errors were 5.8% and 0.7%, only three spectra were misclassified over the 429 spectra of the test set. This large improvement obtained with machine learning techniques was uniform for all molecules but maximal for Bevacizumab with an 88.3% reduction on combined errors (2.1% versus 17.9%).


Assuntos
Anticorpos Monoclonais/análise , Aprendizado de Máquina , Humanos , Análise de Regressão , Análise Espectral Raman
20.
Presse Med ; 36 Spec No 1: 1S76-81, 2007 Mar.
Artigo em Francês | MEDLINE | ID: mdl-17546773

RESUMO

Due to its high sensitivity and specificity, determination of the c-galactosidase A activity in leukocytes is the gold standard to confirm the diagnosis of Fabry disease in hemizygous moles. In contrast, heterozygous females cannot be dependably diagnosed by this method and genotyping should always be carried out. Two recent breakthroughs have contributed to the rise of screening programs for Fabry disease: first, the use of filter papers to collect blood or urine spots from individuals in at-risk populations for Fabry disease, second, the development of moss spectrometry Substrate accumulation and enzyme activity can be measured on urine and blood samples, respectively Moss spectrometry allows the qualitative and quantitative determination of the accumulation of the undegraded substrate (globotriaosylceromide) in urine, but also the measurement of enzyme activities in blood samples for the simultaneous diagnosis of several inborn errors of metabolism, among which lysosomal storage diseases and in particular Fabry disease.


Assuntos
Doença de Fabry/diagnóstico , Doença de Fabry/genética , Humanos , Espectrometria de Massas , Triexosilceramidas/análise , Triexosilceramidas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA