Mário Sérgio Piantavini

Insulin analogues versus human insulin in type 1 diabetes: direct and indirect meta-analyses of efficacy and safety

All patients with Diabetes Mellitus (DM) receive insulin therapy. In this study, we evaluated the efficacy, safety and tolerability of human insulin and insulin analogues. We performed a systematic review of the literature and a meta-analysis according to the Cochrane Collaboration methodology. In the absence of clinical studies comparing insulins, we performed a mixed treatment comparison to establish the differences between the active treatments. We included studies published from 1995 to 2010. HbA1c results, episodes of hypoglycemia and nocturnal hypoglycemia data were extracted and analyzed. Thirty-five randomized clinical trials were selected after examining the abstract and a full text review. These studies included 4,206 patients who received long-acting insulin analogues and 5,733 patients who received short-acting insulin analogues. Pooled data regarding efficacy indicated no significant differences in HbA1c values between glargine or detemir (once daily) and NPH insulin. However, a twice-daily dose of detemir produced differences in HbA1c values that favored detemir (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I2=0%). Direct and indirect comparisons are consistent and show that there were no significant differences between human insulin and insulin analogues in efficacy or safety. Our results indicate that long- and short-acting insulin analogues offer few clinical advantages over conventional human insulin.

Chemometric quality inspection control of pyrantel pamoate, febantel and praziquantel in veterinary tablets by mid infrared spectroscopy.

This paper describes the development and validation of a new multivariate calibration method based on diffuse reflectance mid infrared spectroscopy for direct and simultaneous determination of three veterinary pharmaceutical drugs, pyrantel pamoate, praziquantel and febantel, in commercial tablets. The best synergy interval partial least squares (siPLS) model was obtained by selecting three spectral regions, 3715-3150, 2865-2583, and 2298-1733 cm(-1), preprocessed by first derivative and Savitzky-Golay smoothing followed by mean centering. This model was built with five latent variables and provided root mean square errors of prediction (RMSEP) equal or lower than 0.69 mg per 100 mg of powder for the three analytes. The method was validated according the appropriate regulations through the estimate of figures of merit, such as trueness, precision, linearity, analytical sensitivity, bias and residual prediction deviation (RPD). Then, it was applied to three different veterinary pharmaceutical formulations found in the Brazilian market, in a situation of multi-product calibration, since the excipient composition of these commercial products, which was not known a priori, was modeled by an experimental design that scanned the likely content range of the possible constituents. The results were verified with high performance liquid chromatography with diode array detection (HPLC-DAD) and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and were in agreement with the predicted values at 95% confidence level. The developed method presented the advantages of being simple, rapid, solvent free, and about ten times faster than the HPLC ones.

Rapid detection of aspergillosis in immunocompromised patients using DIMS and chemometric analysis

Rapid diagnosis of aspergillosis is one of the most important aspects for disease control and treatment. The purpose of this study was to develop a metabolic fingerprint of serum from immunocompromised patients that can enable rapid detection of aspergillosis. Serum samples from immunocompromised patients with and without aspergillosis were analyzed by direct infusion mass spectrometry (DIMS). Data from the mass spectra were subjected to chemometric analysis using principal component analysis and partial least squares-discriminant analysis. Our method was able to efficiently distinguish patients with and without aspergillosis and predict the presence or absence of aspergillosis in unknown samples. Therefore, DIMS along with chemometric analysis seems to be a promising technique for rapid diagnosis of aspergillosis.

Elucidation of the electronic spectrum changes of KA-Al3+ complex by potentiometric titration, FTIR, 13C RMN and Quantum Mechanics

Mário S. Piantavinia, Alan G. Gonçalvesa, Ângela C. L. B. Trindadea, Miguel D. Nosedab, Ana L. R. Mercêc, Antonio E. H. Machadod and Roberto Pontaroloa,* Departamento de Farmácia, Universidade Federal do Paraná, 80210-170 Curitiba – PR, Brasil Departamento de Bioquímica, Universidade Federal do Paraná, 81531-990 Curitiba – PR, Brasil Departamento de Química, Universidade Federal do Paraná, 81531-990 Curitiba – PR, Brasil Instituto de Química, Universidade Federal de Uberlândia, 38400-902 Uberlândia – MG, Brasil

Simultaneous Determination of Antimalarial Agents by LC-MS/MS and Its Application to Evaluation of Fixed-Dose Tablets

We developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify the antimalarials artesunate (ARS) and mefloquine (MFQ) in fixed-dose tablets. The detection was performed by a triple-quadrupole mass spectrometer in multiple reaction monitoring (MRM) in positive ion mode via electrospray ionization. Chromatographic separation was achieved with an XBridge C18 column (50 × 2.1 mm, 5 μm), using isocratic elution (350 μL min-1) of water/acetonitrile/methanol (30:35:35, v/v/v) containing 0.1% formic acid. The method was validated according to the International Conference of Harmonization (ICH) guidelines. The calibration curves obtained for ARS (400 to 600 ng mL-1) and MFQ (800 to 1200 ng mL-1) showed good linearity (r2 > 0.99), precision (relative standard deviation (RSD): ARS < 2.0%; MFQ < 1.9%), and accuracy (recoveries: ARS, 102.4-103.4%; MFQ, 97.4-101.6%), and were stable for 24 h at 8 oC. The method was successfully applied to commercial tablets, and recoveries of 98.7 ± 4.7% (ARS) and 105.6 ± 3.13% (MFQ). The method developed is a reliable alternative for public quality inspection control with the advantage of tandem mass specificity and speed.

Comparison between Ultraviolet and Infrared Spectroscopies for the Simultaneous Multivariate Determination of Pyrantel and Praziquantel

Methods based on multivariate calibration and diffuse reflectance infrared Fourier transform (DRIFT) and ultraviolet (UV) spectroscopies were developed for the simultaneous determination of two veterinary pharmaceutical drugs, pyrantel pamoate and praziquantel, in commercial tablets. The best UV model was obtained with the full spectra, 200-400 nm, and partial least squares (PLS). The best DRIFT model was optimized by selecting the most predictive spectral regions with synergy interval PLS, 3998-3636 cm-1, 3274-1824 cm-1 and 1100-735 cm-1. Both methods were validated according to Brazilian and international guidelines through the estimate of figures of merit, such as trueness, precision, linearity, analytical sensitivity, bias and residual prediction deviation (RPD). These methods were applied to the determination of the drugs in three different veterinary formulations commercialized in the Brazilian market and the results were compared with high performance liquid chromatography (HPLC). DRIFT was considered more suitable for the quality control of these formulations, because it is faster, does not use solvents and does not generate chemical waste.

SIMULTANEOUS SPECTROPHOTOMETRIC DETERMINATION OF PYRANTEL PAMOATE AND FEBANTEL IN PHARMACEUTICAL PREPARATIONS USING PARTIAL LEAST-SQUARES REGRESSION

The multivariate spectroscopic determination of the combination of pyrantel pamoate (PP) and febantel (FB) in pharmaceutical preparations was carried out by partial least-squares regression. The UV absorbance spectra of standard mixtures of PP and FB were measured at concentrations ranging from 5.76–11.52 and 6–12 μg/mL, respectively, in a diluent solution of methanol and acetonitrile. The best model was selected with variable selection (280–320, 380–400 nm), 2 latent variables and mean centered. External validation was performed using 13 different mixtures, which provided prediction errors lower than 1%. The method was validated in accordance with international and Brazilian guidelines. This method was successfully employed to quantify the drug content in two different pharmaceutical formulations (solid — capsules, liquid — oral suspensions) with good prediction capacity. Furthermore, its advantages include the use of simple and accessible reagents and equipment, and a low operating cost.