Quetiapine is an atypical antipsychotic used to treat schizophrenia. However, despite great interest for its chronic therapeutic use, quetiapine has some important side effects such as weight gain induction. The development of a quetiapine nanocarrier can potentially target the drug into central nervous system, resulting in a reduction of systemic side effects and improved patient treatment. In the present work, a simple liquid chromatography/ultraviolet detection (LC/UV) analytical method was developed and validated for quantification of total quetiapine content in lipid core nanocapsules as well as for determination of incorporation efficiency. An algorithm proposed by Oliveira et al. (2012) was applied to characterize the distribution of quetiapine in the pseudo-phases of the nanocarrier, leading to a better understanding of the quetiapine nanoparticles produced. The analytical methodology developed was specific, linear in the range of 0.5 to 100 µg mL−1 (r2 > 0,99), and accurate and precise (R.S.D < ±5%). The absolute recovery of quetiapine from the nanoparticles was approximately 98% with an incorporation efficiency of approximately 96%. The results indicated that quetiapine was present in a type III distribution according to the algorithm, and was mainly located in the core of the nanoparticle because of its logD in the formulation pH (6.86 ± 0.4).

A simple HPLC/UV method was developed for the determination of the anticancer candidate LaSOM 65 in rat plasma. Samples were cleaned by protein precipitation with acetonitrile (recovery > 95%), after which they were subjected to chromatography under the isocratic elution of an acetonitrile:water (45:55, ν/ν) solution with detection at 303 nm. The method was linear (r² > 0.98) over the concentration range (0.05-2 µg mL-1) with intra- and inter-day precision ranging from 9.6% to 13.6% and 4.3% to 5.4%, respectively. The accuracy of the method ranged from 85% to 113.6%, and it showed sufficient sensitivity to determine pharmacokinetic parameters of LaSOM 65 after intravenous administration to Wistar rats.

In spite of different methods reported in the literature to determine olanzapine in biological fluids, all of them used high volumes of plasma. Therefore, the purpose of this paper was to develop an LC-MS/MS method using small plasma volume (0.1 mL) to apply in a preclinical pharmacokinetic investigation. The method was linear over the concentration ranges of 10 - 1000 ng mL-1. Extraction recoveries, stability, and validation parameters were evaluated. Results were within the acceptable limits of international guidelines. A significant decrease in clearance led to a significant 2.26-times increase in AUC0 - 6h of olanzapine-loaded lipid-core nanocapsules compared with free-olanzapine.

A rapid HPLC analytical method was developed and validated for the determination of the N-phenylpiperazine derivative LASSBio-579in plasma rat. Analyses were performed using a C18 column and elution with 20 mM sodium dihydrogen phosphate monohydrate - methanol. The analyte was monitored using a photodiode array detector (257 nm). Calibration curves in spiked plasma were linear over the concentration range of 0.3-8 mg/mL with determination coefficient > 0.99. The lower limit of quantification was 0.3 mg/mL. The applicability of the HPLC method for pharmacokinetic studies was tested using plasma samples obtained after administration of LASSBio-579 to Wistar rats, showing the specificity of the method.

O objetivo deste trabalho foi o duplo pico observado no perfil farmacocinético plasmático da ranitidina após administração oral a voluntários sadios através de análise compartimental. Uma dose simples de 300 mg de ranitidina foi administrada a dez voluntários sadios (5 homens e 5 mulheres). Amostras de sangue foram coletadas em diferentes tempos e analisadas por HPLC. Os perfis plasmáticos foram avaliados pela abordagem compartimental e nãocompartimental. Os parâmetros não compartimentais determinados foram k (0,0054 ± 0,001 min¹), t² (2,2 ± 0,4 h), Vd/F (265,3 ± 70,6 L), Cl/F (84,8 ± 24,3 L/h) e AUC (225916 ± 54099 ng*min/mL). A análise compartimental foi conduzida utilizando-se o modelo de dois compartimentos corporais com constantes de absorção de primeira ordem a partir de dois sítios de absorção diferentes. Os parâmetros determinados foram k21 (0,0149 ± 0,0133 min¹), k a1 (0,0117 ± 0,0073 min¹), k a02(0,1496 ± 0,1699 min¹), Vc (128 ± 75,2 L), a (0,0299 ± 0,0319 min¹), b (0,0074 ± 0,0014 min¹) e o tempo para o início da absorção no segundo sítio (126,7 ± 58,1 min). O modelo usado na análise compartimental foi adequado para descrever o duplo pico no perfil plasmático da ranitidina e para determinar os parâmetros farmacocinéticos.

The aim of this study was to describe the double peak plasma pharmacokinetic profile of ranitidine after oral administration to healthy volunteers using non-compartmental and compartmental analysis. A single 300 mg dose of ranitidine was given to ten healthy volunteers (5 male and 5 female). Blood samples were drawn at different times and analyzed by HPLC. Plasma profiles were evaluated by non-compartmental and compartmental approaches. The non-compartmental parameters determined were k (0.0054 ± 0.0010 min-1), t1/2ss/F (265.3 ± 70.6 L), Cl/F (84.8 ± 24.3 L/h) and AUC (225916 ± 54099 ng*min/mL). The compartmental analysis was carried out using a two compartments body model, with first order absorption from two different sites. The parameters determined were k21 (0.0149 ± 0.0133 min-1), k a1(0.0117 ± 0.0073 min-1), k a2 (0.1496 ± 0.1699 min-1), Vc (128 ± 75.2 L), a (0.0299 ± 0.0319 min-1), b (0.0074 ± 0.0014 min-1) and time for the beginning of the absorption from the second site (126.7 ± 58.1 min). The model used in the compartmental analysis was adequate to describe the double peak of ranitidine plasma profile and to determine the pharmacokinetic parameters.