High-performance liquid chromatographic determination of d-/l-epinephrine enantiomer ratio in lidocaine-epinephrine local anesthetics.
A procedure for the determination of the ratio of d- to l-epinephrine in lidocaine-epinephrine local anesthetics is described. Epinephrine was isolated via Sep-Pak cartridges and derivatized with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate; the d- and l-chiral derivatives were separated and measured by high-performance liquid chromatography. About 70 samples of various dosage forms and concentrations from four manufacturers were successfully analyzed by the method.
Development and validation of a chiral LC method for analysis of the four stereoisomers of 1045U85 in plasma.
A method for analysis of the four stereoisomers of 1045U85 in rat plasma was developed and validated. The method involved liquid extraction of 1045U85 and an internal standard (propranolol) from plasma, followed by reaction with a chiral derivatizing reagent, GITC. The diastereoisomeric products were then separated by reversed-phase LC. The range of quantitation was 9.828-0.121 micrograms ml-1 for total 1045U85 (3.440-0.042 micrograms ml-1 for the RR and SS isomers, and 1.474-0.018 micrograms ml-1 for the RS and SR isomers). Specificity of the method for 1045U85 was demonstrated using spiked plasma samples as well as plasma samples from dosed animals. Extraction recovery of 1045U85 and propranolol was greater than 95%, and the derivatization reaction was shown to be complete. Accuracy (% bias) ranged from -2.6 to 3.9% for total 1045U85 and from -4.7 to 14.1% for the individual stereoisomers. Precision (% RSD) was 3.8-8.7% for total 1045U85 and 2.9-16.5% for the individual isomers. Plasma samples stored at -70 degrees C were stable for 19 weeks. The method has been used to determine plasma 1045U85 concentrations in nonclinical studies with this compound.
Synthesis of 2,4-dideoxy-.beta.-D-erythro-hexopyranosyl nucleosides
The synthesis of 1-(2,4-dideoxy-β-D-erythro-hexopyranosyl)thymine (12) 1 was accomplished using two different synthetic routes. It was obtained starting either from 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose or from tri-O-acetyl-D-glucal. The other modified nucleosides, with either a cytosine, guanine, or adenine moiety, were synthesized using the second reaction scheme. Deoxygenation reactions were accomplished with the (2,4-dichlorophenoxy)thiocarbonyl derivatives generated in situ