Development of a novel method of misoprostol detection on filter paper: Proof-of-concept

Purpose: Uteronics are critical to managing and treating postpartum hemorrhaging (PPH), the global leading cause of maternal mortality that kills 800 women daily. While oxytocin is a widely used uteronic, misoprostol has been used in some low-resource countries as it is significantly cheaper, easier to administer, and not reliant on a cold chain. However, recent studies suggest that degradation of misoprostol tablets is accelerated if exposed to humidity at any point during manufacture. State-of-the-art means of assessing misoprostol quality involve high performance liquid chromatography (HPLC), which is expensive and requires high technical skill. Therefore, there is a need for a low-cost, light-weight, and easy-to-use alternative for quality testing. We investigated the use of enzymatic-based assays, which are widely used in point-of-care analysis but has not been studied for misoprostol. Methods: We hypothesized that misoprostol, which contains a secondary alcohol, could be selectively metabolized by alcohol dehydrogenase. Two methods were developed to assess the feasibility to detect pure misoprostol in aqueous solution: a previously-developed amperometric assay on paper-screen printed electrodes, and a colorimetric test. Approximate binding constants were estimated and the accuracy of misoprostol quantification was compared to that measured by HPLC. Results: Pure misoprostol in both a standard acetonitrile/water mixture and aqueous solution was quantified with high sensitivity by HPLC. The accuracy of misoprostol detection by the amperometric method was 87.1 ± 2.3% (n = 3). Conclusions: Based on this proof-of-concept study, enzymatic-based assays for misoprostol quantification can be considered as a novel method for low-cost and point-of-care quality testing. Further development is warranted to optimize the accuracy and sensitivity of this method for tablet products. © 2016, Korean Society of Medical and Biological Engineering and Springer.