M.C.B.S.M. Montenegro

Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment

Pharmaceuticals are biologically active and persistent substances which have been recognized as a continuing threat to environmental stability. Chronic ecotoxicity data as well as information on the current distribution levels in different environmental compartments continue to be sparse and are focused on those therapeutic classes that are more frequently prescribed and consumed. Nevertheless, they indicate the negative impact that these chemical contaminants may have on living organisms, ecosystems and ultimately, public health. This article reviews the different contamination sources as well as fate and both acute and chronic effects on non-target organisms. An extensive review of existing data in the form of tables, encompassing many therapeutic classes is presented.

Modeling, Structural, and Spectroscopic Studies of Lanthanide-Organic Frameworks

In this paper, we report the hydrothermal synthesis of three lanthanide-organic framework materials using as primary building blocks the metallic centers Eu(3+), Tb(3+), and Gd(3+) and residues of mellitic acid: [Ln(2)(MELL)(H(2)O)(6)] (where Ln(3+) = Eu(3+), Tb(3+), and Gd(3); hereafter designated as (1), (2) and (3)). Structural characterization encompasses single-crystal X-ray diffraction studies, thermal analysis, and vibrational spectroscopy, plus detailed investigations on the experimental and predicted (using the Sparkle/AM1 model) photophysical luminescent properties. Crystallographic investigations showed that the compounds are all isostructural, crystallizing in the orthorhombic space group Pnnm and structurally identical to the lanthanum 3D material reported by the group of Williams. (2) is highly photoluminescent, as confirmed by the measured quantum yield and lifetime (37% and 0.74 ms, respectively). The intensity parameters (Omega(2), Omega(4), and Omega(6)) of (1) were first calculated using the Sparkle/AM1 structures and then employed in the calculation of the rates of energy transfer (W(ET)) and back-transfer (W(BT)). Intensity parameters were used to predict the radiative decay rate. The calculated quantum yield derived from the Sparkle/AM1 structures was approximately 16%, and the experimental value was 8%. We attribute the registered differences to the fact that the theoretical model does not consider the vibronic coupling with O-H oscillators from coordinated water molecules. These results clearly attest for the efficacy of the theoretical models employed in all calculations and open a new window of interesting possibilities for the design in silico of novel and highly efficient lanthanide-organic frameworks.

Flow-injection amperometric determination of dopamine in pharmaceuticals using a polyphenol oxidase biosensor obtained from soursop pulp

The amperometric determination of dopamine (Do) in pharmaceuticals formulations by flow injection analysis (FIA) is proposed. An enzymatically modified carbon paste electrode constituted by 25% (w/w) of polyphenol oxidase obtained from Annona muricata L. tissue, 30% (w/w) of graphite, 30% (w/w) of silicone and 15% (w/w) of 7,7,8,8 tetracyanoquinodimethane (TCNQ), was used as flow-through detector. The flow amperometric detection was carried out at a potential of 0.10 V (vs. Ag/AgCl) when an injected sample volume of 250 microl was inserted on a 0.3 M phosphate buffer carrier solution (pH 7.8) flowing at 2.5 ml/min. The developed biosensor showed good stability and reproducibility, enabling up to 500 determinations in 60 days, without considerable loss of enzymatic activity. The FIA system presented a linear response to Do concentrations in the interval from 2 x 10(-2) to 2 x 10(-4) M, with relative standard deviations lower than 1.5%. The kinetic parameter K(M) for the soluble and immobilized enzyme was 1.45 x 10(-2) and 1.91 x 10(-2) M, respectively. In the analyses of different commercially pharmaceutical formulations a relative deviation lower than about 3.4% was obtained.

Dopamine Ion-Selective Electrode for Potentiometry in Pharmaceutical Preparations

Abstract This paper reports the construction and evaluation of a dopamine sensitive electrode and its usefulness for the determination of this compound by direct potentiometry in pharmaceutical preparations. The electrode comprised a carboxylated poly(vinyl chloride) membrane based on β-cyclodextrine dissolved in 2-fluoro-2-nitrodiphenyl ether and using tetrakis(p-chlorophenyl) borate as a fixed anionic site. For comparison purposes membranes with similar composition but including normal high molecular weight PVC were also prepared.The electrodes including carboxylated poly(vinyl chloride) presented linear response within the concentration range of 5×10−5 and 10−1 mol dm−3 of dopamine with a slope of about 59 mV decade−1 of activity, in the pH range of 2 to 7.5 units. The response time was less than 15 seconds. Selectivity coefficients for different interferents including sodium, potassium, ammonium, lithium, epinephrine and norepinephrine were evaluated using the separated solution method and no significant interferences were observed. The electrode displays useful analytical characteristics for the direct determination of dopamine in pharmaceutical preparations. Results with an average recovery of 98.6±0.3% were obtained.

Sequential potentiometric determination of chloride and nitrate in meat products

Abstract The analytical control of chloride and nitrate in meat products is important. For this reason in this work a sequential method for their determination by using chloride- and nitrate-selective electrodes has been developed. The extraction of both ions was carried out by stirring the samples for 30 min in a hot 5.0 × 10 −2 mol litre −1 sulphuric acid solution. Direct potentiometry for chloride and multiple standard additions for nitrate were used as analytical techniques of measurement. The mean coefficient of variation and the average percentage of spike recoveries calculated for the chloride determination in five different meat products were 0.68% and 101%, respectively. For the nitrate determination these data were 0.84% and 101%, respectively. The limits of detection were 71.0 mg kg −1 and 23.2 mg kg −1 for chloride and nitrate, respectively. The mean chloride and nitrate concentrations determined by application of the developed method to 50 samples of meat products were found to be 21.1 g kg −1 and 133.5 mg kg −1 , respectively. Throughout the study, the Volhard titration for determination of chloride and the brucine spectrophotometric method for determination of nitrate, adopted as reference methods, were used simultaneously. Comparison of variances and linear regression analysis of the results obtained were carried out to validate the proposed sequential potentiometric method.

Exploiting sequential injection analysis with lab-on-valve and miniaturized potentiometric detection Epinephrine determination in pharmaceutical products.

Miniaturized potentiometric units were constructed, evaluated and incorporated in a SIA-LOV manifold in order to the control of pharmaceutical analysis. The method validation was done with ephinefrine determinations in commercial pharmaceutical products. The optimization procedures were directed at potential versus epinephrine concentration. This approach was achieved by selecting 60cm of reactor and a flow rate of 11muLs(-1) and injecting 78muL of epinephrine standard solutions in a 1.0x10(-3)molL(-1) IO(4)(-) solution. A linear range was found for epinephrine concentrations between 2.0x10(-4) and 2.5x10(-3)molL(-l) with a slope of 35528mVLmol(-l) and r(2)=0.997. Under these conditions the analytical results for the commercial pharmaceutical formulations of 0.908 and 0.454mgmL(-1), respectively, with a R.S.D. of 0.34 for both, was obtained. Through down scaling periodate-selective electrode it was possible to benefit from the recognized advantages of the lab-on-valve sequential-injection based systems, namely regarding equipment portability, reduced consumption of the sample and the reagents and the reduction of effluent waste. Furthermore, the new periodate electrode configuration is easy to achieve in common laboratories and enables the implementation of low volume detection cell where the electrical noise, that is frequently presented in potentiometric based procedures, is significantly reduced.

A flow-batch internal standard procedure for iron determination in hydrated ethanol fuel by flame atomic absorption spectrometry.

A flow-batch manifold coupled to a flame atomic absorption spectrometer was evaluated to assess the iron content by the internal standard method in hydrated ethanol used as fuel in automotive industry. For this assessment official methods require calibration procedures with matrix matching, making it difficult to obtain accurate results for samples adulterated by the addition of water. Nickel was selected as the internal standard since it is usually absent in samples and because it requires similar conditions of atomization. After procedure optimization, which requires about 4.25mL of sample and standard per measurement, it was possible to get linear analytical response for iron concentrations between 0.12 and 1.40mgL(-1) and a detection limit of 0.04mgL(-1). Eighteen samples were collected randomly from fuel stations in Pernambuco (Brazil) and iron concentration was determined using the proposed procedure. Comparison of results obtained (0.20-1.50mgL(-1)) showed a mean standard error of 3.9%, with 3.8% and 2.3% calculated for the mean variation coefficients of the proposed method and the reference procedure, respectively. For adulterated samples (0.12-0.64mgL(-1)), the mean standard error was 4.8% when compared with the standard addition method. These results allowed concluding that the proposed procedure is adequate to accomplish the determination of iron in ethanol fuel in a large scale basis with a sampling rate of about 10h(-1).

Fast and sensitive UHPLC methods with fluorescence and tandem mass spectrometry detection for the determination of tetracycline antibiotics in surface waters.

In this paper two fast and highly sensitive ultra-high performance liquid chromatography (UHPLC) methods for the determination of tetracycline antibiotics (oxytetracycline, tetracycline, doxycycline, demeclocycline, chlortetracycline, minocycline and degradation product epitetracycline) in surface waters have been developed using fluorescence (FL) and mass spectrometry (MS) detection. ACQUITY UPLC BEH C8 and ACQUITY CSH C18 columns were employed for FL and MS detection, respectively, both packed with 1.7μm particles. Mixed-mode separation mechanism of CSH (charged surface technology) sorbent was found particularly useful in analysis of TCs, which possess problematic amphoteric structures. The FL methodology was based on chelation of tetracyclines with calcium ions to perform on-column derivatisation. The developed methods were compared in the terms of validation parameters including linearity, sensitivity, precision and accuracy. The linearity range for FL detection was within 7ngmL(-1) to 50μgmL(-1) with method limit of detection (MLOD) as low as 0.2ngmL(-1) for most of the analytes. MS detection showed even higher sensitivity reaching MLOD of 0.003ngmL(-1), which is the highest sensitivity reported so far in analysis of TCs. Matrix matched calibration curves in the range of 0.01-50ngmL(-1) were used for quantification to compensate for matrix effects with the correlation coefficients demonstrating good linearity (0.9940-0.9999). The extraction of the antibiotics from surface waters was performed using solid phase extraction with Oasis HLB cartridges. Accuracy was expressed as recovery with values ranging from 96.52% to 127.30% and from 91.66% to 123.70% for FL and MS detection, respectively.

Cyclodextrin-based potentiometric sensors for midazolam and diazepam.

In this work the implementation of benzodiazepine ion-selective electrodes for pharmaceutical formulations control is described. The solid-contact electrodes for midazolam and diazepam are based on polymeric membranes incorporating respectively beta-cyclodextrin and (2-hydroxiproyl)-gamma-cyclodextrin as ionophores, 2-fluorophenyl 2-nitrophenyl ether as plasticizer and potassium tetrakis (p-chlorophenyl) borate as ionic additive. For conventionally shaped midazolam electrode a slope of 61.9+/-1.3 mVdec(-1), a LLLR of 5.7+/-2.7 x 10(-4)gL(-1) and pH range of 2.6-5.4 was obtained, while the corresponding values for diazepam electrodes were of 67.6+/-3.0 mVdec(-1), 4.9+/-1.5 x 10(-2)gL(-1) and 1.9-2.7 pH units, respectively. Membrane optimization was based on the molar ratio between the ionophore and additive for midazolam and on inclusion cavity of cyclodextrin for diazepam. The miniaturization of the above-described electrodes gave rise to potentiometric detectors for sequential-injection lab-on-valve system with similar characteristics albeit the useful lifetime shortened from 1 year to approximately 15 days under continuous operation. The optimized flow conditions were achieved for sample injection volumes of 20 microL propelled towards the detection cell at the flow rate of 16 microLs(-1) during 80s. Real sample analysis revealed statistical accuracy and between-days precision comparable to the general used chromatographic-based procedure.

Multi-task flow system for potentiometric analysis: its application to the determination of vitamin B6 in pharmaceuticals.

A flow set-up based on the sequential injection analysis concept was designed, aiming at increased automation and robustness of procedures related with potentiometric detection in pharmaceutical control. In this sense, programmable set-up calibration, ion-selective electrode characterization, standard addition techniques and titration procedures could be carried out without any stock solutions conventional handling or modification on the physical structure of the flow system. Evaluation of a flow-through vitamin B6 selective electrode and its application to routine analysis of pharmaceuticals were selected as models to demonstrate the system potentialities. The system ability to generate in-line calibrating solutions was verified by comparing the results with those obtained with solutions prepared by the manual procedure. The vitamin B6 determination in pharmaceutical products was carried out and in-line performed recoveries gave values within 97.4-103.5%. The system ability to perform titrations was ascertained using the precipitation reaction of vitamin B6 with tetraphenylborate. Other profitable features such as lower reagent consumption with a low effluent generation volume were also achieved.