Method development for the enantiomeric purity determination of low concentrations of adrenaline in local anaesthetic solutions by capillary electrophoresis.
L-adrenaline is often included in local anaesthetic (LA) solutions for injection to improve the quality of the anaesthetic block. The concentration of the LA is between 2.5 and 20 mg/ml and the concentration of adrenaline is typically < or = 0.1% of the LA concentration. In order to follow the racemization into d-adrenaline, not only is chiral separation needed but also sufficient resolution from the LA and other components of the injection solution. Furthermore, very high sensitivity is needed in order to be able to determine the d-enantiomer at very low concentrations, i.e. down to about 0.1 microg/ml. The development of a chiral capillary electrophoresis method that is able to determine the racemization of adrenaline is described, together with a limited validation. Samples are injected without pretreatment and analysed with a capillary electrophoresis buffer containing 40 mM heptakis(2,6-di-O-methyl)-beta-cyclodextrin, 0.10 M phosphoric acid and 0.05 M triethanolamine. The amounts of d-adrenaline found in the LA products tested were typically < 3% of the l-adrenaline concentration and < 0.003% of the LA concentration.
Sänger-van de Griend
Cari E
CE
Analytical Development, Pharmaceutical and Analytical R&D, AstraZeneca, SE-151 85 Södertälje, Sweden. cari.sanger@astrazeneca.com
Ek
Anders G
AG
Widahl-Näsman
Monica E
ME
Andersson
E K Margareta
EK
D000777:Anesthetics / Q000032:analysis* / Q000737:chemistry; D002045:Bupivacaine / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003505:Cyclodextrins / Q000032:analysis / Q000494:pharmacology; D004573:Electrolytes / Q000737:chemistry; D019075:Electrophoresis, Capillary / Q000379:methods*; D004837:Epinephrine / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008619:Mepivacaine / Q000494:pharmacology; D008956:Models, Chemical; D011318:Prilocaine / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013678:Technology, Pharmaceutical / Q000379:methods
D000777:Anesthetics; D003505:Cyclodextrins; D004573:Electrolytes; D011318:Prilocaine; D008619:Mepivacaine; D002045:Bupivacaine; D004837:Epinephrine