Multicriteria optimization methodology was applied in development of UHPLC-UV-MS method for separation of cilazapril, hydrochlorothiazide and their degradation products. This method is also applicable for analysis of cilazapril, hydrochlorothiazide and their degradation products in combined tablet formulation. Prior to method optimization forced degradation studies were conducted. Cilazapril and hydrochlorothiazide were subjected to acidic (0.1, 0.5 and 1.0 M HCl), basic (0.1, 0.5 and 1.0 M NaOH), thermal (70°C), oxidative (3-30% H2O2) degradation and photodegradation (day light). Cilazapril appeared to be unstable toward acid and base and resulted in formation of cilazaprilat. Hydrochlorothiazide significantly degraded after acid, base and thermal hydrolysis and formed degradation product was 4-amino-6-chlorobenzene-1.3-disulfonamide. For both substances, after oxidative degradation unknown products have arisen. Initial percentage of acetonitrile in mobile phase, final percentage of acetonitrile in mobile phase, time of gradient elution and column temperature were defined as variables to be optimized toward two chromatographic responses by means of central composite design and Derringer's desirability function. The satisfactory chromatographic analysis was achieved on Kinetex C18 (2.6 µm, 50 × 2.1 mm) column with temperature set at 25°C. The final mobile phase consisted of acetonitrile and 20 mM ammonium formate buffer (pH adjusted to 8.5). The flow rate of the mobile phase was 400 μL min-1 and it was pumped in a gradient elution mode.
Resorting to complementary/alternative medical (CAM) therapies can lead to bad health outcomes or interfere with officially recommended therapies. CAM use is, nevertheless, widespread and growing. This could be partially due to the perception of the CAM industry as powerless and non-profit oriented, in contrast to the pharmaceutical industry (“Big Pharma”). In reality, both industries are highly profitable and powerful; to highlight this similarity, science communicators coined the term “Big Suppla”. Drawing from the sample of 242 participants upon all exclusions, we experimentally tested whether varying these attributes in presenting the industries impacts consumers’ evaluation of the two categories of products (herbs and supplements) and their willingness to try and recommend them. We also tested whether the effect is moderated by conspiratorial thinking, and whether it is due to a change in trust. All hypotheses were pre-registered. As expected, participants who read the Big Suppla vignette decreased the endorsement of both supplements and herbs, whilst, in contrast to our hypotheses, there were no significant changes in endorsement in the Baby Suppla group. Conspiratorial thinking was related to more endorsement of CAM, but it did not moderate the experimental effects. We also did not observe the expected mediation by trust. Our most robust results corroborate the idea that challenging the myth of benevolence of the CAM industry makes people more critical in evaluating its products or considering their usage. They support the intuitions of science communicators who coined the term Big Suppla, and can help in tailoring public health messages.
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