Determination of Simvastatin in Pharmaceutical Dosage Forms by Optimized and Validated Method Using HPLC/UV

Simvastatin belongs to the group of anticholesterol agents used in the treatment of hypercholesteraemia. Analytical methods used to determine the concentration of this active pharmaceutical ingredient (API), in dosage forms in the quality tests, are commonly based on high performance liquid chromatography (HPLC) and should be fast and reliable. The purpose of this study was to compare and validate two methods of analysis of simvastatin using HPLC and different eluent mixtures: acetonitrile/water vs. methanol/ water in gradient elution. Several columns were tested at different temperatures. However satisfied peak shapes and validation parameters were obtained for both methods. The one using methanol as an eluent was chosen for the determination of simvastatin in dissolution tests, mostly due to lower price of the eluent

Determination of Simvastatin in Pharmaceutical Dosage Forms by Optimized and Validated Method Using HPLC/UV

Simvastatin belongs to the group of anticholesterol agents used in the treatment of hypercholesteraemia. Analytical methods used to determine the concentration of this active pharmaceutical ingredient (API), in dosage forms in the quality tests, are commonly based on high performance liquid chromatography (HPLC) and should be fast and reliable. The purpose of this study was to compare and validate two methods of analysis of simvastatin using HPLC and different eluent mixtures: acetonitrile/water vs. methanol/ water in gradient elution. Several columns were tested at different temperatures. However satisfied peak shapes and validation parameters were obtained for both methods. The one using methanol as an eluent was chosen for the determination of simvastatin in dissolution tests, mostly due to lower price of the eluent

Experimental and Genomic Evaluation of the Oestrogen Degrading Bacterium Rhodococcus equi ATCC13557

Rhodococcus equi ATCC13557 was selected as a model organism to study oestrogen degradation based on its previous ability to degrade 17α-ethinylestradiol (EE2). Biodegradation experiments revealed that R. equi ATCC13557 was unable to metabolise EE2. However, it was able to metabolise E2 with the major metabolite being E1 with no further degradation of E1. However, the conversion of E2 into E1 was incomplete, with 11.2 and 50.6% of E2 degraded in mixed (E1-E2-EE2) and E2-only conditions, respectively. Therefore, the metabolic pathway of E2 degradation by R. equi ATCC13557 may have two possible pathways. The genome of R. equi ATCC13557 was sequenced, assembled, and mapped for the first time. The genome analysis allowed the identification of genes possibly responsible for the observed biodegradation characteristics of R. equi ATCC13557. Several genes within R. equi ATCC13557 are similar, but not identical in sequence, to those identified within the genomes of other oestrogen degrading bacteria, including Pseudomonas putida strain SJTE-1 and Sphingomonas strain KC8. Homologous gene sequences coding for enzymes potentially involved in oestrogen degradation, most commonly a cytochrome P450 monooxygenase (oecB), extradiol dioxygenase (oecC), and 17β-hydroxysteroid dehydrogenase (oecA), were identified within the genome of R. equi ATCC13557. These searches also revealed a gene cluster potentially coding for enzymes involved in steroid/oestrogen degradation; 3-carboxyethylcatechol 2,3-dioxygenase, 2-hydroxymuconic semialdehyde hydrolase, 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase, 3-(3-hydroxy-phenyl)propionate hydroxylase, cytochrome P450 monooxygenase, and 3-oxosteroid 1-dehydrogenase. Further, the searches revealed steroid hormone metabolism gene clusters from the 9, 10-seco pathway, therefore R. equi ATCC13557 also has the potential to metabolise other steroid hormones such as cholesterol

A quantitative structure-biodegradation relationship (QSBR) approach to predict biodegradation rates of aromatic chemicals

The objective of this work was to develop a QSBR model for the prioritization of organic pollutants based on biodegradation rates from a database containing globally harmonized biodegradation tests using relevant molecular descriptors. To do this, we first categorized the chemicals into three groups (Group 1: simple aromatic chemicals with a single ring, Group 2: aromatic chemicals with multiple rings and Group3: Group 1 plus Group 2) based on molecular descriptors, estimated the first order biodegradation rate of the chemicals using rating values derived from the BIOWIN3 model, and finally developed, validated and defined the applicability domain of models for each group using a multiple linear regression approach. All the developed QSBR models complied with OECD principles for QSAR validation. The biodegradation rate in the models for the two groups (Group 2 and 3 chemicals) are associated with abstract molecular descriptors that provide little relevant practical information towards understanding the relationship between chemical structure and biodegradation rates. However, molecular descriptors associated with the QSBR model for Group 1 chemicals (R2 = 0.89, Q2loo = 0.87) provided information on properties that can readily be scrutinised and interpreted in relation to biodegradation processes. In combination, these results lead to the conclusion that QSBRs can be an alternative tool to estimate the persistence of chemicals, some of which can provide further insights into those factors affecting biodegradation

Fate of four Different Classes of Chemicals Under Aerobic and Anaerobic Conditions in Biological Wastewater Treatment

The removal mechanisms and extent of degradation of 28 chemicals (triclosan, fifteen polycyclic aromatic hydrocarbons, four estrogens, and eight polybrominated diphenyl ether congeners) in different biological treatment systems [activated sludge, up-flow anaerobic sludge blanket reactor (UASB) and waste stabilization pond (WSP)] was investigated to provide insights into the limits of engineered biological treatment systems. This was done through degradation experiments with inhibition and abiotic controls in static reactors under aerobic and anaerobic conditions. Estrogens showed higher first order degradation rates (0.1129 h−1) under aerobic conditions with activated sludge inocula followed by low molecular weight (LMW) PAHs (0.0171 h−1), triclosan (0.0072 h−1), middle (MMW) (0.0054 h−1) and high molecular weight PAHs (HMW) (0.0033 h−1). The same trend was observed under aerobic conditions with a facultative inoculum from a WSP, although at a much slower rate. Biodegradation was the major removal mechanism for these chemicals in the activated sludge and WSP WWTPs surveyed. Photodegradation of these chemicals was also observed and varied across the group of chemicals (estrogens (light rate = 0.4296 d−1; dark = 0.3900 d−1) degraded faster under light conditions while reverse was the case for triclosan (light rate = 0.0566 d−1; dark = 0.1752 d−1). Additionally, all the chemicals were resistant to anaerobic degradation with UASB sludge, which implies that their removal in the UASB of the surveyed WWTP was most likely via sorption onto solids. Importantly, the first order degradation rate determined in this study was used to estimate predicted effluent concentrations (PECs). The PECs showed good agreement with the measured effluent concentrations from a previous study for these treatment systems

Survivin expression at the mRNA level in tumors and the protein concentration in the serum and peritoneal fluid in patients with serous ovarian tumors

Objectives: Ovarian cancer is one of the gynecological cancers that have the worst prognosis. The expression of the proteins from the IAP family (inhibitor of apoptosis protein), including survivin, is observed in many types of cancer. The aim of the study was to evaluate survivin at the mRNA level in tumors and the protein concentration in the serum and peritoneal fluid of patients with serous ovarian cancer in order to assess the relationship between the concentration of survivin and the histological subtypes of cancer. Material and methods: The study group consisted of 55 women, including patients with serous ovarian cancer (n = 30, nine low-grade serous carcinoma LGSC, 21 high-grade serous carcinoma HGSC), serous cysts (n = 10) and the control group (n = 15). The concentration of protein in the peritoneal fluid and serum was assessed using ELISA tests. The expression of survivin gene BIRC5 in the tumors was assessed using the RT-qPCR method. Results: The data that was obtained indicated that the concentration of survivin was higher in the serum of the women with serous ovarian cancer compared those that had benign tumors (p < 0.05) and the control group (p < 0.001). The survivin concentration was also higher in both the serum and peritoneal fluid in the HGSC group compared to the LGSC group (p < 0.001). The mRNA level was highest in the HGSC group, and there was a statistically significant difference compared to those in the benign tumor group and HGSC group ( p < 0.05). Conclusions: The observed changes prove that the expression level increases significantly in HGSC in both the protein and mRNA levels. Based on these findings, it can be assumed that assessing this parameter could be a useful additional indicator of the progression and differentiation of this type of cancer. However, this requires further research in a larger group of patients and possibly in other types of ovarian cancer