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Endemic in more than 90 countries and territories, malaria is the most widely, populational, and geographically, parasitic disease in the world. Plasmodium sp. resistance to available drugs is one of the biggest problems for malaria eradication. In this study, we develop a method for the simultaneous determination of two new derivatives of betulinic and ursolic acids with antimalarial activity designated 3-O-butanoylbetulinic and 3-O-butanoylursolic acids. An analytical method was developed by high-performance liquid chromatography coupled, in series, to ultraviolet (UV) and charged aerosol (CAD) detectors. The chromatographic system, operated isocratically by reversed-phase, consisted in a mobile phase composed of acetonitrile: water pH 3.0 adjusted with formic acid (85:15, v/v), flow rate of 1.2 mL/min and a PhenoSphere Next octadecylsilane column (250 mm x 4.6 mm, 5 μm particle size). Chromatograms were recorded simultaneously in UV and CAD, at a concentration of 50 µg mL-1, an injection volume of 20 μL at a controlled temperature of 50 °C. The method was found to be selective, linear (r > 0.99), precise (RSD < 2.0%), accurate, and robust for both analytes, and considered statistically validated, and can be applied to the identification and quantification of these new drug candidates.

Immunosuppressive therapy is used in solid organ transplant treatment, and mycophenolic acid (MPA) is one of the immunosuppressive drugs most used worldwide. It is a potent, selective, non-competitive, and reversible inosine monophosphate dehydrogenase (IMPDH) inhibitor that acts to inhibit guanine synthesis. To improve solubility, MPA is used as the prodrug mycophenolate mofetil (MMF) or as an enteric-coated mycophenolate sodium salt (EC-MPS). It is metabolized into mycophenolic acid phenyl glucuronide (MPAG), the inactive and major metabolite, and into acyl glucuronide (AcMPAG), pharmacologically active. In kidney transplantation, combined immunosuppressive therapy with cyclosporine (CsA) and tacrolimus (Tac) is widely used, showing beneficial effects. This paper aimed to review papers published in the last two decades and discuss factors that can interfere with the pharmacokinetics of MPA. Data collected confirm that MPA plasma levels should be monitored to evaluate immunosuppressive therapy since pharmacokinetics can be influenced by factors such as interpatient variability, coadministration of other immunosuppressive agents, post-transplant period, renal function, and dose. However, to perform drug monitoring, costs and facility may be limitations. Monitoring MPAG together with MPA would be a great improvement in therapy as it represents a big part of MPA levels and can be related to the increase of adverse effects.

Fetal exposure to illicit drugs is a worldwide problem, since many addicted women do not stop using it during pregnancy. Cocaine consumed in powdered (snorted or injected) or smoked (crack cocaine) form are harmful for the baby and its side effects are not completely known. Meconium, the first stool of a newborn, is a precious matrix usually discarded, that may contain amounts of substances consumed in the last two trimesters of pregnancy. Analyzing this biological matrix it is possible to detect the unaltered molecule of cocaine (COC) or its metabolite benzoylecgonine (BZE) and pyrolytic products anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC). A liquid chromatography mass spectrometry (LC-MS) method was validated for meconium samples after solvent extraction, followed by direct injection of 10μL. Linearity covered a concentration range of 15 to 500ng/mg with a lower limit of quantification (LLOQ) of 15ng/mg for all analytes. Matrix effect was evaluated and showed adequate results. Detection of illicit substances usage can be crucial for the baby, since knowing that can help provide medical care as fast as possible. The method proved to be simple and fast, and was applied to 17 real meconium samples.

A method was developed using hydrophilic interaction liquid chromatography (HILIC), a versatile mode of liquid chromatography, to determine cocaine, its main degradation products, benzoylecgonine and ecgonine, main pyrolytic products, anhydroecgonine and anhydroecgonine methyl ester, to be used as standards, and a frequent contaminant, levamisole. Detection of all compounds was achieved using two detectors connected in series: charged aerosol detector (CAD) and ultraviolet detector (UV). No method was found in the literature using HILIC coupled to CAD and UV to determine these compounds. The method was carried out with a Phenomenex Kinetex HILIC (150 mm × 4.6 mm ID; 2,6 µm) column with mobile-phase acetonitrile: 10 mM ammonium acetate pH 6.3 (75:25 v/v) with flow rate 0.8 mL min−1 and oven temperature set at 30 °C. CAD detection was performed using a nitrogen pressure of 35 psi, range of 100 pA and the UV detection at 200 nm. Validation parameters such as selectivity, linearity, precision and accuracy were evaluated. Methods were successfully validated to detect and quantify all related substances.

A method to assay cocaine (COC), its metabolites benzoylecgonine (BZE), ecgonine (ECG), ecgonine methyl esther (EME), and benzoylnorecgonine (BNE), pyrolytic products anhydroecgonine (AEC) and anhydroecgonine methyl ester (AEME) and adulterant levamisole (LEV) was developed and validated by liquid chromatography-mass spectrometry (LC-MS) using a chemometric approach including a two-level factorial design in the screening step and face-centered central composite design (FCCCD) to achieve the optimization. The method was carried out on positive electrospray ionization (ESI+) with a flow of 1 mL min−1 in isocratic mode consisting of 53% methanol and 47% ammonium acetate 10 mmol L−1 pH 6.3. The chromatographic separation was obtained with a Phenomenex Luna C18(2) column (250 mm × 4.6 mm, particle size 5 μm), with the temperature set at 31 °C. Validation parameters such as specificity, linearity, precision and accuracy were evaluated. The method was linear over the concentration range of 1–100 ng mL−1 for COC, AEME, EME, LEV, BZE and ECG and 5–100 ng mL−1 for AEC and BNE. The method was successfully applied to identify and quantify the analytes.

A reversed-phase ion-pairing liquid chromatographic method was developed and validated for the assay of Fe(II) in ferrous bisglycinate (Fe-bis-gly) capsules using 4-(2-pyridylazo) resorcinol reagent. The analysis was carried out using a Gemini RP-18 (150 mm × 4.6 mm I.D., particle size 5 μm) analytical column; the mobile phase consisted of a mixture of acetonitrile–water (28:72 v/v) containing 1 mM tetrabutylammonium hydrogensulfate and 1% phosphate buffer (pH 8.0). The flow rate was 1.0 mL min−1 and the detection was achieved with a photodiode array (PDA) detector at 706 nm. The specificity of the method was proved using stress conditions and evaluated using a PDA detector. The data validation showed that the method is specific, fast, accurate, and reproducible for the determination of Fe-bis-gly in dosage form. The response was linear over a range of 1.0–2.6 μg mL−1 (r = 0.9999). The accuracy of the method ranged from 98.02 to 102.75%. The RSD values for intra- and inter-day precision studies were below 1.3 and 1.1%, respectively. There was no interference of the excipients on the determination of the active pharmaceutical ingredient.

Este trabalho se propõe a analisar a novela Leutnant Gustl (1900), de Arthur Schnitzler. A obra, o primeiro monólogo interior em língua alemã, foi escrita no fin-de-siècle em Viena, período conhecido por sua alta produtividade intelectual e artística. Como consequência de uma política mesclada entre a monarquia e burguesia, a regência da cidade era caracterizada por um hibridismo de valores, a priori, paradoxos. Esse composto heterogêneo se reflete na sociedade e na classe artística, resultando em uma produção na qual elementos modernos e pré-modernos díspares convivem. Nesse sentido, sempre considerando o objeto como ponto de partida da análise, será observado em que medida a novela representa a pré-modernidade, com traços como a defesa da honra e a prática do duelo, e outros tipicamente modernos, como a ascensão do lazer, o consumo massificado e a valorização do individualismo. É nesse cenário que examinaremos o tenente Gustl, personagem-narrador, por muitos teóricos considerado um tipo representante do indivíduo da sociedade vienense daquela época. Tomando sua personalidade e sua trajetória como eixo norteador desse estudo, tentaremos mostrar em que medida ele se configura como um indivíduo moderno, apesar de sustentar, externamente, uma fachada de valores prémodernos, os quais, por meio do monólogo interior, o leitor sabe não se tratar nada além de uma imagem. Assim, tomando Gustl como um representante de seu tempo, contraditório e zeloso das falsas aparências, será investigada a sua inserção como indivíduo no seu tempo. This dissertation aims to analyze the novel Leutnant Gustl (1900), by Arthur Schnitzler. The novel, the first to employ the \"stream-of-consciousness\" technique in German, was written in fin-de-siècle Vienna, a period known for its high intellectual and artistic productivity. Owing to a merged policy between the monarchy and the bourgeoisie, the citys government was characterized by a hybridization of values, paradoxical a priori. This heterogeneous compound is reflected in society and the artistic community, resulting in a production in which modern and pre-modern different elements coexist. Thereby, always considering the object as a starting point of analysis, there will be seen to what extent the novel represents the premodern with traits like the defense of honor and the practice of dueling , and other typically modern, as the rise of leisure, the massive consumption and the awareness of individualism. It is in this background that we examine the lieutenant Gustl, character and narrator, by many experts considered a representative of the individual type of Viennese society at the time. Taking his personality and his career as a core line, this study attempts to show the extent to which he is configured as a modern individual, in spite of sustaining, externally, an artificial appearance of pre-modern values, which, through interior monologue, the reader knows it is nothing but a façade. Hence, taking Gustl as a representative of his time, contradictory and earnest of false appearances, it will be investigated his inclusion as an individual in his time.

Drug abuse by nursing mothers is an ongoing concern because it may cause many adverse effects to the newborns. The development of analytical methods to analyze drugs of abuse in colostrum (first milk produced after birth) has a huge importance, because it enables the monitoring and the correct follow-up to users and newborns. A liquid chromatography mass spectrometry (LC–MS) method was developed and validated for the determination of cocaine and smoked cocaine (crack) biomarkers in colostrum. Cocaine (COC) and its major metabolite benzoylecgonine (BZE), the pyrolytic products anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC) were analyzed after a simple protein precipitation procedure using atropine (ATP) as internal standard (IS). Applying a chemometric approach study, all peaks were chromatographically separated at isocratic condition with a Kinetex HILIC column for polar compounds, at 30 °C in 12 min. One ion was detected for the quantification and three ions for confirmation of each analyte. The method was linear for all analytes in the concentration range of 5–300 ng/mL with correlation coefficients ( r ) between 0.9983 and 0.9996. The lower limit of quantification (LLOQ) was 5 ng/mL with acceptable validation parameters. Matrix effect was assessed by post-extraction addition approach and showed good results, demonstrating that protein precipitation cleaning procedure is fast, reliable and demand small quantities of organic solvent. The LC–MS method is fast and cheap compared to other equipments and was also successfully applied to assess real samples of colostrum from nursing mothers who were suspect of cocaine/crack abuse.

A stability-indicating method using MEKC was validated for the analysis of olmesartan medoxomil in tablets. Successful separation was achieved using a fused silica capillary (40 cm x 50 µm i.d.); background electrolyte consisted of a combination of 10 mmol L-1 borate buffer and 5 mmol L-1 anionic detergent sodium dodecyl sulfate (95:5; v/v) pH 6.5; hydrodynamic mode at 50 mBar for 5 s; 25 kV separation voltage at 25 ºC; and column temperature 25 ºC with detection at 257 nm. The proposed method, validated following ICH guidelines, was applied to the determination of this antihypertensive with good results compared with an LC method.

Natural products are the most important source of antitumor and anti-infective agents, at the same time, they can have problems related to their physic-chemical parameters resulting in poor pharmacokinetic. Semi- synthesis promotes structural changes which can improve activity and pharmacokinetic properties and decreases toxicity. The aim of this review is demonstrate the importance of semi- synthesis to obtain new drugs as antineoplastics (ixabepilone, temsirolimus, everolimus, vinflunine and trabectine), antimicrobials (telavancin, oritavancin, tigecicline, dalbavancin and telitromicine) and antifungals (andidulafungine and micafungine). 10.5216/ref.v9i1.17776