title: Development and validation of LC methods for the separation of misoprostol related substances and diastereoisomers.
abstract: Misoprostol is a synthetic prostaglandin E1 analogue which is mainly used for prevention and treatment of gastric ulcers, but also for abortion due to its labour inducing effect. Misoprostol exists as a mixture of diastereoisomers (1:1) and has several related impurities owing to its instability at higher temperatures and moisture. A simple and robust reversed phase liquid chromatographic (RPLC) method is described for the separation of the related substances and a normal phase (NP) LC method for the separation of misoprostol diastereoisomers. The RPLC method was performed using an Ascentis Express C18 (150 mm × 4.6 mm, 5 μm) column kept at 35 °C. The mobile phase was a gradient mixture of mobile phase A (ACN-H2O-MeOH, 28:69:3 v/v/v) and mobile phase B (ACN-H2O-MeOH, 47:50:3 v/v/v) eluted at a flow rate of 1.5 mL/min. UV detection was performed at 200 nm. The NPLC method was undertaken by using an XBridge bare silica (150 mm × 2.1 mm, 3.5 μm) column at 35 °C. The mobile phase contained 1-propanol-heptane-TFA (4:96:0.1%, v/v/v), pumped at a flow rate of 0.5 mL/min. UV detection was performed at 205 nm. This LC method can properly separate the two diastereoisomers (Rs > 2) within an analysis time of less than 20 min. Both methods were validated according to the ICH guidelines. Furthermore, these new LC methods have been successfully applied for purity control and diastereoisomers ratio determination of misoprostol bulk drug, tablets and dispersion.
authors.affiliation: KU Leuven, University of Leuven, Department of Pharmaceutical & Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, O&N2, PB 923, B-3000 Leuven, Belgium; Mekelle University, College of Health Sciences, Department of Pharmacy, P.O. Box 1871, Mekelle, Ethiopia.
authors.forename: Getu
authors.initials: G
authors.lastname: Kahsay
authors.affiliation: KU Leuven, University of Leuven, Department of Pharmaceutical & Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, O&N2, PB 923, B-3000 Leuven, Belgium.
authors.forename: Huiying
authors.initials: H
authors.lastname: Song
authors.affiliation: KU Leuven, University of Leuven, Department of Pharmaceutical & Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, O&N2, PB 923, B-3000 Leuven, Belgium.
authors.forename: Fran
authors.initials: F
authors.lastname: Eerdekens
authors.affiliation: KU Leuven, University of Leuven, Department of Pharmaceutical & Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, O&N2, PB 923, B-3000 Leuven, Belgium.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Tie
authors.affiliation: KU Leuven, University of Leuven, Department of Pharmaceutical & Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, O&N2, PB 923, B-3000 Leuven, Belgium.
authors.forename: Danny
authors.initials: D
authors.lastname: Hendriks
authors.affiliation: KU Leuven, University of Leuven, Department of Pharmaceutical & Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, O&N2, PB 923, B-3000 Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Van Schepdael
authors.affiliation: KU Leuven, University of Leuven, Department of Pharmaceutical & Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, O&N2, PB 923, B-3000 Leuven, Belgium.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Cabooter
authors.affiliation: KU Leuven, University of Leuven, Department of Pharmaceutical & Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, O&N2, PB 923, B-3000 Leuven, Belgium. Electronic address: Erwin.Adams@pharm.kuleuven.be.
authors.forename: Erwin
authors.initials: E
authors.lastname: Adams
mesh_terms: D000433:1-Propanol / Q000737:chemistry; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D004340:Drug Contamination; D016595:Misoprostol / Q000032:analysis* / Q000737:chemistry*; D015203:Reproducibility of Results; D013607:Tablets / Q000032:analysis / Q000737:chemistry
chemical_list: D013607:Tablets; D016595:Misoprostol; D000433:1-Propanol
keywords: Diastereoisomers; Impurities; Liquid chromatography; Method development; Misoprostol