A green approach for the quantification of daptomycin in pharmaceutical formulation by UV spectrophotometry

abstract Daptomycin is the first approved drug from a new class of antimicrobials, the cyclic lipopeptides, and is a very important antimicrobial agent in current clinical practice. Currently, there are no "green" analytical methods described in the literature to analyze the typical pharmaceutical dosage form of daptomycin. Thus, the aim of this work was to validate an environment-friendly spectrophotometric method in the UV region, for the analysis of daptomycin as a lyophilized powder. Water was used as diluent and the analyses were carried out on a spectrophotometer at 221 nm. The method met all validation requirements of the ICH guidelines, over a concentration range of 6-21 µg mL-1. A Student's t-test demonstrated that the proposed method was comparable to an HPLC method previously validated. Thus, the validated spectrophotometric method could quantify daptomycin in a powder form for injectable solutions, while being an economical, rapid, and "green" alternative for routine analysis in quality control

Comparative evaluation of seven resistance interpretation algorithms and their derived genotypic inhibitory quotients for the prediction of 48 week virological response to darunavir-based salvage regimens

Background: the darunavir genotypic inhibitory quotient (gIQ) has been suggested as one of the predictors of virological response to darunavir-containing salvage regimens. Nevertheless, which resistance algorithm should be used to optimize the calculation of gIQ is still debated. The aim of our study was to compare seven different free-access resistance algorithms and their derived gIQs as predictors of 48 week virological response to darunavir-based salvage therapy in the clinical setting. Methods: patients placed on two nucleoside reverse transcriptase inhibitors\u200a+\u200a600/100 mg of darunavir/ritonavir twice daily \u200a\ub1\u200a enfuvirtide were prospectively evaluated. Virological response was assessed at 48 weeks. Darunavir resistance interpretation was performed according to seven different algorithms, of which two were weighted algorithms. Analysis of other factors potentially associated with virological response at 48 weeks was performed. Results: fifty-six treatment-experienced patients were included. Overall, 35 patients (62.5%) had a virological response at 48 weeks. Receiver operator characteristic curve analysis showed that De Meyer's weighted score (WS) and its derived gIQ (gIQ WS) were the most accurate parameters defining virological response, and related cut-offs showed the best sensitivity/specificity pattern. In univariate logistic regression analysis, baseline log viral load (P = 0.028), optimized background score 65 2 (P = 0.048), WS >5 (P = 0.001) and WS gIQ 65 600 (P\u200a<\u200a0.0001) were independently associated with virological response. In multivariate analysis, only baseline log viral load (P = 0.008) and WS gIQ 65 600 (P < 0.0001) remained in the model. Conclusions: in our study, although different resistance interpretation algorithms and derived gIQs were associated with virological response, gIQ WS was the most accurate predictive model for achieving a successful virological response

Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c) (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product) and Levaquin(c) (Janssen-Cilag Farmacêutica Ltda, Brazil, test product) was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c) and Levaquin(c) are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies

Application of an electronic nose coupled with fuzzy-wavelet network for the detection of meat spoilage

Food product safety is one of the most promising areas for the application of electronic noses. During the last twenty years, these sensor-based systems have made odour analyses possible. Their application into the area of food is mainly focused on quality control, freshness evaluation, shelf-life analysis and authenticity assessment. In this paper, the performance of a portable electronic nose has been evaluated in monitoring the spoilage of beef fillets stored either aerobically or under modified atmosphere packaging, at different storage temperatures. A novel multi-output fuzzy wavelet neural network model has been developed, which incorporates a clustering pre-processing stage for the definition of fuzzy rules. The dual purpose of the proposed modelling approach is not only to classify beef samples in the relevant quality class (i.e. fresh, semi-fresh and spoiled), but also to predict their associated microbiological population. Comparison results against advanced machine learning schemes indicated that the proposed modelling scheme could be considered as a valuable detection methodology in food microbiology

ELISA-based detection of gentamicin and vancomycin in protein-containing samples

BACKGROUND: Orthopaedic implant infections are treated by surgical debridement, systematic antibiotic treatment or local antibiotic treatment with antibiotic-loaded beads. Currently antibiotic concentrations in wound exudate, serum, urine or tissue samples are determined with HPLC or fluorescent spectrometric assays. Both methods are heavily influenced due to proteins in the samples. QUESTIONS/PURPOSES: Is ELISA capable to detect gentamicin and vancomycin in protein-containing samples like serum and wound exudate. METHODS: Two specific competitive ELISA-assays were set-up to detect either gentamicin or vancomycin in protein-rich samples. An antibiotic-BSA hapten was generated as a coatable antigen and commercially available antibodies were applied for downstream immunodetection. RESULTS: The developed ELISAs perform at a detection range of 2–500 ng/ml gentamycin and 20–5000 ng/ml vancomycin. Both ELISAs were capable of detecting these antibiotics in human serum and wound exudate without being compromised by the presence of proteins. We did not detect cross-reactivity for gentamicin in the vancomycin ELISA or vice versa. CONCLUSIONS: The antibiotic ELISAs detect gentamicin and vancomycin at low concentrations in protein-rich samples and they can be used as a high throughput and cost-effective alternative for chromatographic or fluorescent methods. CLINICAL RELEVANCE: These ELISAs can be used to detect very low gentamicin or vancomycin concentrations in clinical samples or assess novel orthopaedic antibiotic release systems in in vitro and in vivo studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1411-y) contains supplementary material, which is available to authorized users