| Enantioseparations of a series of chiral drugs collected in Ch.P2010wereinvestigated using chiral stationary phase (CSP), chiral mobile phase additive (CMPA)and chiral derivatization reagent (CDR) by high performance liquid chromatography(HPLC). The effects of column temperature, the concentration of alcohol displacer,flow rate and organic acidic and alkaline modifier in mobile phase were studied, andthe mechanism of chiral selectors recognizing chiral compounds was discussed.First of all，the study is concerned with the enantiomers separation of twentypharmaceutical racemates collected in Ch.P2010. It was performed on five kinds ofchiral stationary phase of amylose and cellulose ramifications by high performanceliquid chromatographic (HPLC) methods, which was included adrenaline,phenylephrine hydrochloride, salbutamol, procaterol hydrochloride, dipivefrinehydrochloride, isoprenaline hydrochloride, clorprenaline hydrochloride, nisoldipine,tropicamide, indapamide, pantoprazole sodium, flurbiprofen, dioxopromethazinehydrochloride, promethazine hydrochlorine, propafenone hydrochloride, miconazolenitrate, econazole nitrate, chlorthalidone, carvedilol, sotaol hydrochloride andphenoxybenzamine hydrochloride. The racemates were separated on Chiralcel OJ–Hcolumn, Chiralcel OD-H column, Chiralpak AD-H column, ChiralpakAS-H columnand ChiralpakIA-H column as stationary phase, and the mobile phase consisted ofisopropanol and n-hexane. The flow rate was set at0.6mL/min. The enantiomersseparations of these twenty racemates on Chiralcel OJ-H column, Chiralcel OD-Hcolumn, Chiralpak AD-H column, Chiralpak AS-H column and Chiralpak IA-Hcolumn were studied, while the effects of column temperature, the concentration of alcohol displacer, flow rate and organic acidic and alkaline modifier in mobilephase were investigated. Procaterol hydrochloride, isoprenaline hydrochloride,nisoldipine, tropicamide, promethazine hydrochlorine, miconazole nitrate,chlorthalidone and phenoxybenzamine hydrochloride had good separations with a pairof enantiomers on OJ-H column, but salbutamol, clorprenaline hydrochloride,dioxopromethazine hydrochloride and sotaol hydrochloride were not separatedentirely with the resolution value of1.4,0.4,0.3and1.1. The chromatographicseparations on Chiralcel OD-H column were very different from that on ChiralcelOJ-H column. Salbutamol, isoprenaline hydrochloride, dioxopromethazinehydrochloride, propafenone hydrochloride, nisoldipine, tropicamide, miconazolenitrate, phenoxybenzamine hydrochloride, adrenaline and phenylephrinehydrochloride could be separated completely with a pair of peaks of enatiomers.Isoprenaline hydrochloride, clorprenaline hydrochloride, indapamide, pantoprazolesodium, propafenone hydrochloride, miconazole nitrate, econazole nitrate, sotaolhydrochloride were able to be separated completely with a pair of peaks ofenantiomers on AS-H column and while carvedilol and promethazine hydrochlorinewith a resolution value of1.2and0.46only. Salbutamol, dipivefrine hydrochloride,clorprenaline hydrochloride, tropicamide, dioxopromethazine hydrochloride,propafenone hydrochloride, pantoprazole sodium and chlorthalidone were able to beseparated completely with a pair of peaks of enantiomers on IA-H column.Nisoldipine, indapamide, econazole nitrate, carvedilol and sotaol hydrochloride canbe separated only with a resolution value of0.81,0.2,1.35,0.43and0.68only.Salbutamol, clorprenaline hydrochloride, tropicamide, dioxopromethazinehydrochloride, propafenone hydrochloride, adrenaline and phenylephrinehydrochloride were able to be separated completely with a pair of peaks ofenantiomers on AD-H column. The results indicated that twenty chiral drugs could beseparated on chiral stationary phase of polysaccharide in normal phasechromatographic system. The chromatographic retention and resolution ofenantiomers could be adjusted by factors including column temperature, theconcentration of alcohol displacer, flow rate and organic acidic and alkaline modifier in mobile phase. It was shown that the resolution was improved with reducingconcentration of alcohol displacer or reducing of flow rate. The drugs had betterresolution at column temperature of30℃.Moreover, the enantiomers of eighteen chiral drugs were separated individuallyusing chromatographic methods in this essay. Firstly, the research of resolution ofsix pharmaceutical racemates collected in Ch.P2010with high performance liquidchromatography using sulfobutylethe-β-cyclodextrin (SBE-β-CD) as mobile phaseadditive were studied. Isoprenaline hydrochloride, clorprenaline hydrochloride,tropicamide, promethazine hydrochlorine and carvedilol were able to be separatedcompletely with a pair of peaks of enantiomers on C18column with SBE-β-CD.Salbutamol can be separated only with a resolution value of1.19only. The factorssuch as concentration of SBE-β-CD, percentage of alcohol displacer, additive oftriethylamine in the mobile phase, pH value, and the temperature of chromatographiccolumn and et. al were investigated and the mechanism of separation was discussed.Finally, the enantiomers of thirteen chiral drugs were separated individuallyusing chromatographic methods in this essay. Firstly, the research of resolution offour pharmaceutical racemates collected in Ch.P2010with high performance liquidchromatography using2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate(GITC). Dipivefrine hydrochloride, clorprenaline hydrochloride, propafenonehydrochloride and carvedilol were able to be separated completely with a pair ofpeaks of enantiomers on C18column. The effects of type of alcohol displacer,triethylamine and molar ratio of the reaction on the separation were investigated.The results of the enantiomers separation collected in Ch.P2010by using threekinds of high performance liquid chromatography are as follows. Twenty enantiomerswere able to be separated completely with a pair of peaks of enantiomers on at leastone column. The effect of chiral stationary phase of amylose and celluloseramifications is complementary. Sulfobutylethe-β-cyclodextrin (SBE-β-CD) asmobile phase additive was suitable for the separation of N contained alkalinecompounds.2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC) wassuitable for the separation of amine compounds. |
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