Method to determine stability and recovery of carboprost and misoprostol in infusion preparations.
The two synthetic prostaglandin analogues, carboprost and misoprostol, are used extensively in obstetric and gynaecological practice. Our recent research of these compounds' use for intra-umbilical injection to treat adherent placenta necessitated their storage in solution for 3-4 days. This raised concerns over the stability and applied dosage in the in-house infusion preparations. It requires various pharmacological preparations before administration in clinical practice. We used LCMS to develop a simultaneous, valid, fast and simple method to assess the stability and recovery of their in-house preparations in different conditions. The linearity between 0-40 microg/ml was above 0.995. The reproducibility (CV) was within 5.2%. The limit of quantitation of the method for both compounds is about 2 microg/ml. The accuracy of both compounds from 0.4-40 microg/ml is 96.4-104.3% while the precision is 0.4-7.4%. The recoveries of carboprost in the infusion were from 100.3+/-4.0 to 102.4+/-1.6% and that of misoprostol in Cytotec tablet was from 44.9+/-3.5 to 50.0+/-5.0% in water and saline at 4 degrees C and room temperature. No interference was found from the matrix and between the tested compounds. The compounds were basically stable for 6 days in water and in saline, whether they were stored at 4 degrees C or at room temperature. However, only half of the dosage of misoprostol was recovered in the solution. Therefore, misoprostol dosage should be adjusted before clinical application.
Chu
Kai On
KO
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, NT, Hong Kong.
Wang
Chi Chiu
CC
Pang
Chi Pui
CP
Rogers
Michael Scott
MS
D002138:Calibration; D002260:Carboprost / Q000008:administration & dosage / Q000737:chemistry* / Q000592:standards; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods; D004338:Drug Combinations; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods; D016595:Misoprostol / Q000008:administration & dosage / Q000737:chemistry*; D015394:Molecular Structure; D010120:Oxytocics / Q000008:administration & dosage / Q000737:chemistry; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D011247:Pregnancy; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013696:Temperature; D013997:Time Factors; D014325:Tromethamine / Q000737:chemistry / Q000592:standards
D004338:Drug Combinations; D010120:Oxytocics; D014677:Pharmaceutical Vehicles; D014325:Tromethamine; D016595:Misoprostol; D002260:Carboprost; C062843:carboprost tromethamine