Synthesis and identification of pilocarpic acid diesters, prodrugs of pilocarpine.
A series of new pilocarpic acid diesters were synthesized to obtain prodrugs for pilocarpine with varying physico-chemical properties. Thermospray liquid chromatography-mass spectrometry (TSP-LC-MS), liquid chromatography with UV-detection (LC-UV) and NMR-spectroscopy were used for the identification of the synthetic products and for evaluation of their purity including typical impurities (pilocarpic acid monoester, pilocarpine). TSP-LC-MS-analysis was performed in the reversed-phase mode using acetonitrile (60%)-0.2 M ammonium acetate (40%) as mobile phase. In LC-UV-analysis chromatographic separation was carried out on a reversed-phase column and the mobile phase consisted of methanol (71%) and 0.02 M potassium dihydrogen phosphate, pH 4.5 (29%). Electron ionization-mass spectrometry (EI-MS) was used for elucidation of structures. Elemental compositions of the substances were verified with high resolution-mass spectrometry (HR-MS). The complete establishment of structures presented was based on 1H-, and COSY-NMR-spectroscopy joined to TSP-LC-MS-analysis.
Järvinen
T
T
Department of Pharmaceutical Chemistry, University of Kuopio, Finland.
Auriola
S
S
Peura
P
P
Suhonen
P
P
Urtti
A
A
Vepsäläinen
J
J
D002853:Chromatography, Liquid; D004952:Esters / Q000138:chemical synthesis / Q000302:isolation & purification; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010862:Pilocarpine / Q000031:analogs & derivatives* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000302:isolation & purification
D004952:Esters; D011355:Prodrugs; D010862:Pilocarpine; C029118:pilocarpic acid