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Subcritical fluid chromatography at sub-ambient temperatures for the chiral resolution of ketamine metabolites with rapid-onset antidepressant effects

2019, Hofstetter, Robert K., Potlitz, Felix, Schulig, Lukas, Kim, Simon, Hasan, Mahmoud, Link, Andreas

Chiral metabolites of ketamine exerting rapid-onset yet sustained antidepressant effects may be marketed directly in the future, but require chemo- and enantio-selective chromatographic methods for quality assurance and control. The chromatographic behavior of S-/R-ketamine, S-/R-norketamine, S-/R-dehydronorketamine, and (2R,6R)-/(2S,6S)-hydroxynorketamine in supercritical fluid chromatography (SFC) was investigated computationally and experimentally with the aim of identifying problematic pairs of enantiomers and parameters for chiral resolution. Retention on three different polysaccharide-based chiral stationary phases (Lux Amylose-2, i-Amylose-3, and i-Cellulose-5) provided new information on the significance of halogen atoms as halogen bond donors and hydrogen bond acceptors for enantioselectivity, which could be corroborated in silico by molecular docking studies. Modifiers inversely affected enantioselectivity and retention. Methanol yielded lower run times but superior chiral resolution compared to 2-propanol. Lower temperatures than those conventionally screened did not impair phase homogeneity but improved enantioresolution, at no cost to reproducibility. Thus, sub-ambient temperature subcritical fluid chromatography (SubFC), essentially low-temperature HPLC with subcritical CO2, was applied. The optimization of the SubFC method facilitated the chiral separation of ketamine and its metabolites, which was applied in combination with direct injection and online supercritical fluid extraction to determine the purity of pharmaceutical ketamine formulations for proof of concept. © 2019 by the authors.

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Depression among women of reproductive age in rural Bangladesh is linked to food security, diets and nutrition

2020, Sparling, Thalia M., Waid, Jillian L., Wendt, Amanda S., Gabrysch, Sabine

Objective: To quantify the relationship between screening positive for depression and several indicators of the food and nutrition environment in Bangladesh.Design: We used cross-sectional data from the Food and Agricultural Approaches to Reducing Malnutrition (FAARM) trial in Bangladesh to examine the association of depression in non-peripartum (NPW) and peripartum women (PW) with food and nutrition security using multivariable logistic regression and dominance analysis.Setting: Rural north-eastern Bangladesh.Participants: Women of reproductive age.Results: Of 2599 women, 40 % were pregnant or up to 1 year postpartum, while 60 % were not peripartum. Overall, 20 % of women screened positive for major depression. In the dominance analysis, indicators of food and nutrition security were among the strongest explanatory factors of depression. Food insecurity (HFIAS) and poor household food consumption (FCS) were associated with more than double the odds of depression (HFIAS: NPW OR = 2·74 and PW OR = 3·22; FCS: NPW OR = 2·38 and PW OR = 2·44). Low dietary diversity (<5 food groups) was associated with approximately double the odds of depression in NPW (OR = 1·80) and PW (OR = 1·99). Consumption of dairy, eggs, fish, vitamin A-rich and vitamin C-rich foods was associated with reduced odds of depression. Anaemia was not associated with depression. Low BMI (<18·5 kg/m2) was also associated with depression (NPW: OR = 1·40).Conclusions: Depression among women in Bangladesh was associated with many aspects of food and nutrition security, also after controlling for socio-economic factors. Further investigation into the direction of causality and interventions to improve diets and reduce depression among women in low-and middle-income countries are urgently needed. © © The Authors 2020.