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.
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.
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).
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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Ronsmans C, Graham WJ. Maternal mortality: who, when, where, and why. Lancet. 2006; 368(9542):1189–200.
Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PFA. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006; 367(9516):1066–74.
Maternal mortality fact sheet N°348. World Health Organization. 2014. http://www.who.int/mediacentre/factsheets/fs348/en/. Accessed 22 Oct 2015.
Hofmeyr GJ, Gülmezoglu AM, Novikova N, Linder V, Ferreira S, Piaggio G. Misoprostol to prevent and treat postpartum haemorrhage: a systematic review and meta-analysis of maternal deaths and dose-related effects. Bull World Health Organ. 2009; 87(9):666–7.
Langenbach C. Misoprostol in preventing postpartum hemorrhage:a meta-analysis. Int J Gynaecol Obstet. 2006; 92(1):10–8.
Mehta J, Patidar K, Patel V, Kshatri N, Vyas N. Development & validation of an in vitro dissolution method with HPLC analysis for misoprostol in formulated dosage form. Anal Methods. 2010; 2(1):72–5.
McCrossen SD, Darbyshire-Brown A, Allen C, Carr SA, Brett T. Conf Proc Appropriate Healthcare Technologies for Developing Countries. 2012; 1:1–5
Hall P. Quality of Misoprostol Products (WHO Drug Information Vol. 30, No. 2016. p. 5. http://apps.who.int/medicinedocs/en/m/abstract/Js22361en/. Accessed 22 Oct 2015.
Martinez AW. Microfluidic paper-based analytical devices:from POCKET to paper-based ELISA. Bioanalysis. 2011; 3(23):2589–92.
Liana DD, Raguse B, Gooding JJ, Chow E. Recent advances in paper-based sensors. Sensors. 2012; 12(9):11505–26.
Nie Z, Nijhuis CA, Gong J, Chen X, Kumachev A, Martinez AW, Narovlyansky M, Whitesides GM. Electrochemical sensing in paper-based microfluidic devices. Lab Chip. 2010; 10(4):477–83.
Zhao C, Thuo MM, Liu X. A microfluidic paper-based electrochemical biosensor array for multiplexed detection of metabolic biomarkers. Sci Technol Adv Mater. 2013; 14(5):054402.
Liu H, Xiang Y, Lu Y, Crooks RM. Aptamer-based origami paper analytical device for electrochemical detection of adenosine. Angew Chem Int Ed Engl. 2012; 51(28):6925–8.
Nie Z, Deiss F, Liu X, Akbulut O, Whitesides GM. Integration of paper-based microfluidic devices with commercial electrochemical readers. Lab Chip. 2010; 10(22):3163–9.
Wu G, Zaman MH. Amperometric measurements of ethanol on paper with a glucometer. Talanta. 2015; 134:194–9.
Derman RJ, Kodkany BS, Goudar SS, Geller SE, Naik VA, Bellad MB, Patted SS, Patel A, Edlavitch SA, Hartwell T, Chakraborty H, Moss N. Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial. Lancet. 2006; 368(9543):1248–53.
Challis JR, Patel FA, Pomini F. Prostaglandin dehydrogenase and the initiation of labor. J Perinat Med. 1999; 27(1):26–34.
Johansson A, Mosbach K, Mansson M-O. Horse liver alcohol dehydrogenase can accept NADP+ as coenzyme in high concentrations of acetonitrile. Eur J Biochem. 1995; 227(1-2):551–5.
Chu KO, Wang CC, Pang CP, Rogers MS. Method to determine stability and recovery of carboprost and misoprostol in infusion preparations. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 857(1):83–91.
Rights and permissions
About this article
Cite this article
Wu, G., Gungordu, H.I., Tagontong, N. et al. Development of a novel method of misoprostol detection on filter paper: Proof-of-concept. Biomed. Eng. Lett. 6, 94–99 (2016). https://doi.org/10.1007/s13534-016-0221-7
- Developing countries
- Alcohol dehydrogenase