Determination of drugs in biological matrices is required in different contexts, including development of new drug products, bioequivalence and pharmacokinetic studies, toxicological analysis and ...therapeutic drug monitoring. The presence of endogenous compounds and the analytes low concentration make biological matrices complex to be analyzed. Therefore, sample preparation is an important step. In this context, new extraction techniques have been proposed in recent years. An innovative approach is magnetic solid phase extraction, a new type of solid phase extraction based on magnetic sorbents. This technique has been increasingly studied for determination of drugs in biological matrices due to several advantages over conventional techniques and the development of new materials. Owing to the potential of this approach, the literature was reviewed in order to evaluate the development and application of this technique comprising the period from 2009 to September 2016. Critical evaluation and trends regarding magnetic solid phase extraction were presented.
•Magnetic solid phase extraction (MSPE) has been widely used for drug analysis in biological matrices.•Magnetic nanoparticles surface is easily modified extending the applicability of MSPE.•Materials used in MSPE have high surface area leading to appropriate recoveries.•Innovative materials have been recently developed and applied in MSPE.
The objective of this study was to develop and validate a fast, sensitive and simple liquid chromatography–electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the screening of ...six classes of antibiotics (aminoglycosides, beta-lactams, macrolides, quinolones, sulfonamides and tetracyclines) in fish. Samples were extracted with trichloroacetic acid. LC separation was achieved on a Zorbax Eclipse XDB C18 column and gradient elution using 0.1% heptafluorobutyric acid in water and acetonitrile as mobile phase. Analysis was carried out in multiple reaction monitoring mode via electrospray interface operated in the positive ionization mode, with sulfaphenazole as internal standard. The method was suitable for routine screening purposes of 40 antibiotics, according to EC Guidelines for the Validation of Screening Methods for Residues of Veterinary Medicines, taking into consideration threshold value, cut-off factor, detection capability, limit of detection, sensitivity and specificity. Real fish samples (n=193) from aquaculture were analyzed and 15% were positive for enrofloxacin (quinolone), one of them at a higher concentration than the level of interest (50µgkg−1), suggesting possible contamination or illegal use of that antibiotic.
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•Contamination of fish by antibiotics can lead to serious risks to human health.•Some antibiotics are illegally used in aquaculture.•A screening LC–MS/MS method was developed for 40 antibiotics from 6 classes in fish.
Side effects often limit the use of doxorubicin (DOX) in cancer treatment. We have recently developed a nanostructured lipid carrier (NLC) formulation for synergistic chemotherapy, encapsulating DOX ...and the anticancer adjuvants docosahexaenoic acid (DHA) and α-tocopherol succinate (TS). Hydrophobic ion-pairing with TS allowed a high DOX entrapment in the nanocarrier. In this work, we investigated the pharmacokinetics of this formulation after intravenous administration in mice. The first data obtained led us to propose synthesizing covalent DOX-TS conjugates to increase DOX retention in the NLC. We successfully conjugated DOX to TS via an amide or hydrazone bond. In vitro studies in 4T1 tumor cells indicated low cytotoxicity of the amide derivative, while the hydrazone conjugate was effective in killing cancer cells. We encapsulated the hydrazone derivative in a DHA-based nanocarrier (DOX-hyd-TS/NLC), which had reduced particle size and high drug encapsulation efficiency. The pH-sensitive hydrazone bond allowed controlled DOX release from the NLC, with increased drug release at acidic conditions. In vivo studies revealed that DOX-hyd-TS/NLC had a better pharmacokinetic profile than free DOX and attenuated the short-term cardiotoxic effects caused by DOX, such as QT prolongation and impaired left ventricular systolic function. Moreover, this formulation showed excellent therapeutic performance by reducing tumor growth in 4T1 tumor-bearing mice and decreasing DOX-induced toxicity to the heart and liver, demonstrated by hematologic, biochemical, and histologic analyses. These results indicate that DOX-hyd-TS/NLC may be a promising nanocarrier for breast cancer treatment.
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•Covalent coupling of DOX and TS via amide and hydrazone bonds.•Preparation and characterization of a DHA-based NLC formulation loading the hydrazone conjugate.•DOX-hyd-TS/NLC had better pharmacokinetics than free DOX after intravenous injection in mice.•DOX-hyd-TS/NLC prevented DOX-induced QT prolongation and impairment of left ventricular systolic function.•Administration of DOX-hyd-TS/NLC resulted in high antitumor efficacy and low systemic toxicity in 4T1 tumor-bearing mice.
One of the highest incidences of illegal drug products is related to phosphodiesterase-5 inhibitors, used in treatment of erectile dysfunction, including those containing sildenafil citrate and ...tadalafil. In this context, comprehensive evaluation of the quality of genuine and illegal medicines was performed. A simple and rapid ultra-high performance liquid chromatography (UHPLC-UV) method to quantify sildenafil and tadalafil in the presence of six degradation products was developed and validated. Sildenafil and tadalafil were submitted to forced degradation. The separation was carried out on a Kinetex C18 (50 × 2.1 mm; 1.7 μm) column with mobile phase composed of acetonitrile and aqueous triethylamine solution. The calibration curves were linear in the range of 14-126 μg mL-1 for sildenafil citrate and 4-36 μg mL-1 for tadalafil and the method proved to be selective, precise, accurate and robust. Sildenafil degraded in oxidative media, whereas tadalafil degraded in acidic, alkaline and oxidative environment. The chemical structures and the mechanisms for the formation of the main degradation products were proposed by UHPLC coupled to tandem mass spectrometry. The UHPLC-UV method was applied in the pharmaceutical analysis of genuine and seized medicines. Some of them did not meet quality standards, mainly due to contents below specifications and the large variation on contents between units within a batch.
A simple and sensitive procedure using solid-phase microextraction coupled with high performance liquid chromatography (HPLC) to analyze fluoxetine (FLU) and its metabolite norfluoxetine (nor-FLU) in ...plasma samples was developed and validated. SPME conditions were optimized employing a factorial design. The sampling step was performed using a PDMS-DVB fiber and desorption was carried out in a novel homemade heated interface. Fluoxetine and norfluoxetine were analyzed by HPLC, using a C18 Phase Sep column (150
mm
×
4.6
mm, 3
μm) packed “in house”, and acetonitrile:acetate buffer 25
mmol
l
−1 with triethylamine 25
mmol
l
−1 pH 4.6 (70:30) as the mobile phase. The developed method has shown precision, linearity, specificity, and limit of quantification (LOQ) adequate to assay fluoxetine and norfluoxetine in plasma. Furthermore, the results obtained using the homemade interface has shown an improvement in the desorption process when compared with the results obtained using the off-line mode.
The aim of this study was to develop, characterize and assess the cytotoxic activity of pHsensitive (pHL-Gd), stealth pH-sensitive (SpHL-Gd), and conventional (convL-Gd) liposomes containing ...gadodiamide (Gd-DTPA-BMA).
Formulations were prepared by reverse-phase evaporation method and their physicochemical properties were evaluated by means of particle size, zeta potential, and Gd-DTPA-BMA entrapment. SpHL-Gd was considered being the most promising liposome, since it combines stealth and fusogenic characteristics that might contribute to achieve higher therapeutic efficiency. Their drug encapsulation percentages have been optimized satisfactorily. The addition of Gd-DTPA-BMA at 125 μmol/mL in the SpHL-Gd preparation allowed obtaining liposomes with appropriate encapsulation percentage (20.3 ± 0.1%) and entrapment (25.4 ± 0.1 μmol/mL).
The cytotoxic studies on the 4T1 breast cancer cell line demonstrated that liposomes-loaded with Gd-DTPA-BMA inhibited cancer cell. pHL-Gd and SpHL-Gd liposomes showed higher activity than convL-Gd and free Gd-DTPA-BMA, indicating that the pH-sensitive characteristic was important to improve intracellular delivery.
The presence of polyethylene glycol (PEG) in the SpHL-Gd formulation did not affect the pH-sensitivity and internalization. Therefore, the results of this study suggest the feasibility of liposomes containing Gd-DTPA-BMA as a new promising controlled delivery system.
Prednisone is an anti-inflammatory steroid drug widely used in clinical practice. However, no high-performance liquid chromatographic (HPLC) method has been described in the literature for the ...determination of prednisone in capsules until now. Thus, an HPLC method was developed using a C18 (250x4.0, 5 µm) column, with methanol:water (70:30) as mobile phase at a flow rate of 1 mL/min and detection at 240 nm. The developed method was validated following current Brazilian legislation. Additionally, linearity was assessed by evaluating the assumptions of normality, homoscedasticity, and independency of residuals, and the fit to the linear model. The method showed linearity (r2>0.99) over the range of 14.0-26.0 µg/mL, selectivity, precision (RSD<2.0%), robustness, and accuracy (average recovery of 100.05%). The chromatographic procedure was applied for assay and uniformity content determination of three different batches of prednisone capsules, showing to be suitable for their quality control.
•A method to determine ethylene glycol and diethylene glycol in beer was developed.•The method makes use of the dilution of beer sample and GC–MS.•The method was applied in the analysis of beer ...commercialized in Brazil.•The first report of food contamination with ethylene glycol and diethylene glycol in Brazil.•The first method for simultaneous analysis of ethylene glycol and diethylene glycol in food.
An analytical method for the simultaneous determination of ethylene glycol and diethylene glycol in beer was developed and validated according to current legislation. This method includes the application of sample dilution with ethanol followed by quantification using gas chromatography coupled to mass spectrometry. All figures of merit were within the limits established by regulation. The recoveries of the analytes, expressed as mean recovery, were between 91.9% and 108.9%. Precision, in terms of repeatability and intermediate precision, was established (relative standard deviations were lower than or equal to 10%). The limits of detection (10.0 and 5.0 mg.L−1 for ethylene glycol and diethylene glycol, respectively) and quantification (15.0 mg.L−1 for ethylene glycol and diethylene glycol) obtained were appropriate. Finally, the present method was applied for determination of ethylene glycol and diethylene glycol in 701 beer samples (from 67 different brands and 128 different labels), proving to be reliable.
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