Impurity profiling of morphine by liquid chromatography-heated electrospray ionization mass spectrometry (LC-HESI-MS)

Abstract

Separation of morphine and its impurities (related substances specified in relevant European Pharmacopoeia monographs, as well as the other naturally occurring coextracted alkaloids) was obtained within a close retention window on a reverse phase HPLC column, eluted with optimized gradient, consisting of methanol and 5 mM ammonium formate, adjusted to pH 10.2. Systematic optimization of the chromatographic conditions was carried out using design of experiments. According to their mass spectra, known and specified impurities were identified and tentative structures for unknown impurities were proposed. MS analyses were performed in positive ionization mode using heated electrospray ionization. Fragmentation patterns of the eluted compounds under optimized mass spectrometry conditions indicated that all detected impurities are structurally related to morphine.

Interpol review of controlled substances 2016–2019

“…Morphine: 2016 A voltammetric sensor for determination of paracetamol in the presence of morphine [ 313 ]; a short cascade strategy for the stereoselective synthesis of morphine [ 314 ]; extraction of morphine from poppy seeds [ 315 ]; HPLC method for the simultaneous determination of morphine sulfate and naltrexone hydrochloride content in bulk, solid dosage forms [ 316 ]; life cycle assessment from opium poppy farming to the packaging of morphine [ 317 ]; LC-HRMS for the characterization of transformation products and comparison between irradiated samples and those that have not been irradiated [ 318 ]; determination of Morphine in pharmaceutical products by on-line SPE-HPLC [ 319 ]; 2017 solid state vibrational spectroscopic properties of morphine sulfate pentahydrate studied using FTIR-ATR [ 320 ]; review of the research progress on the synthesis of Morphine alkaloids [ 321 ]; Impurity profiling of morphine by LC-HESI-MS [ 322 ]; design and synthesis of carboxylic group functionalized hollow microporous organic capsules for encapsulation of morphine for prolonged release [ 323 ]; characterization of Morphine, Morphine Hydrochloride, and their Hydrates using 1-dimensional and 2-dimensional solid-state NMR and complemented with powder X-ray diffraction, FTIR, and Raman [ 324 ]; one-pot multicomponent approach to synthesize a new series of morphine derivatives [ 325 ]; high-performance thin-layer chromatography-densitometry method for the quantitative analysis of morphine in the tablets of the Ayurvedic medicines [ 326 ]; tandem Brook rearrangement/silicon Polonovski reaction/fragmentation to give formamide derivatives in moderate yields [ 327 ]; asymmetric total synthesis of (−)-morphine [ 328 ]; stability studies of opioid analgesic, morphine-6-O-sulfate in various buffers and biological matrices and analyzed by HPLC-DAD analysis [ 329 ]; Quantum dots (QDs)-labeled antibody fluorescence immunoassays (FLISA) for the rapid detection of morphine for on-site screening of poppy shell added illegally in hot pot soup base [ 330 ]; rapid construction of the 6/6/5 tricyclic framework via a tandem radical cyclization reaction [ 331 ]; Arymo ER - a new abuse deterrent Morphine formulation [ 332 ]; ALERRT((R)) to quantitative measure the effort required to compromise prescription opioid abuse-deterrent tablets [ 333 ]; comparison of the abuse potential of intact and manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with morphine sulfate ER tablets [ 334 ]; compare abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets [ 335 ]; synthesis of morphinans using a programmed serial stereochemical relay […”