Masaaki Matsuo

Separation and determination of lipophilic corticosteroids and benzothiazepin analogues by micellar electrokinetic chromatography using bile salts.

The separation of corticosteroids and benzothiazepin analogues by micellar electrokinetic chromatography (micellar EKC) was studied in comparison with capillary zone electrophoresis. The separation of these substances was not successful under neutral and alkaline conditions because they migrated with the same velocity as that of the electroosmotic flow. Micellar EKC with sodium dodecyl sulphate (SDS) solutions was also not successful because these substances migrated with almost the same velocity as that of the SDS micelle, owing to their high lipophilicity. The use of bile salts, which have a similar skeleton to corticosteroids, as the micellar phase permitted the separation of these substances with high theoretical plate numbers (150,000-350,000) within a short time (ca. 15 min). Sodium cholate was particularly useful. The effects of bile salt concentration, pH and the addition of methanol were investigated. Micellar EKC was also applied to the determination of the drug substances in tablets and cream using the internal standard method and to purity testing of drug substances and tablets.

Separation and determination of the ingredients of a cold medicine by micellar electrokinetic chromatography with bile salts

The separation of fourteen active ingredients used in a cold medicine was investigated by micellar electrokinetic chromatography (EKC) employing bile salts. Basic drugs were also successfully separated by micellar EKC using bile salts with high theoretical plate numbers (2.0 x 10(5)-3.5 x 10(5)) within a relatively short time (ca. 20 min). The separation of these solutes by micellar EKC was not successful using sodium dodecyl sulphate. The effects of micellar concentration, pH and organic modifier content on migration times and selectivity were investigated. This technique was also applied to the determination of several active ingredients combined in commercial preparations by an internal standard method.

Separation and determination of aspoxicillin in human plasma by micellar electrokinetic chromatography with direct sample injection

Both the separation and determination of aspoxicillin in human plasma by micellar electrokinetic chromatography (MEKC) were investigated. Selectivity in the separation of seven penicillin antibiotics was improved by using MEKC in comparison with capillary zone electrophoresis. Plasma proteins, which might interfere with drug analysis in conventional chromatography, were solubilized by the micelles employed in MEKC and eluted later than the drugs. This permitted the determination of the drugs in plasma by a direct sample injection method. One analysis of a plasma sample was performed within ca. 20 min without pretreatment. Good linearity and recovery were also obtained in the range of plasma levels usually encountered in clinical analysis with a correlation coefficient r = 0.999 and 94-104% recovery. The limit of detection for aspoxicillin was 1.3 micrograms ml-1 at a signal-to-noise ratio of 3.

Separation of corticosteroids and aromatic hydrocarbons by cyclodextrin modified micellar electrokinetic chromatography

Abstract Micellar electrokinetic chromatography (MEKC) permits the separation of uncharged or electrically neutral compounds by the electrophoretic technique, but highly lipophilic compounds, e.g., corticosteroids and aromatic hydrocarbons could not be resolved by MEKC with sodium dodecyl sulfate (SDS) solutions because such solutes migrated with almost the same velocity as that of the SDS micelle, owing to their large micellar solubilization. the addition of cyclodextrins (CDs) to the SDS solution, that is, cyclodextrin-modified micellar electrokinetic chromatography (CD/MEKC), remarkably improved the resolution of these lipophilic compounds. the effects of concentration and the type of CDs on the separation of corticosteroids and aromatic hydrocarbons were investigated.

Chiral separation of trimetoquinol hydrochloride and related compounds by micellar electrokinetic chromatography using sodium taurodeoxycholate solutions and application to optical purity determination

Abstract The chiral separation of trimetoquinol hydrochloride, which is a bronchodilator (Inolin), and three related compounds by micellar electrokinetic chromatography was investigated using a bile salt as a chiral surfactant. Enantiomers of these compounds, except laudanosoline, were successfully separated within 12 min using a separation tube of effective length 500 mm × 0.05 rum i.d. and a 0.05 M sodium taurodeoxycholate solution of pH 7.0. The observed theoretical plate numbers of the peaks were ca. 150000. Chiral recognition was affected by the structure of bile salts, the pH of the buffer solutions used and the structure of the solutes. Of four kinds of bile salts, successful chiral separation was achieved only using sodium taurodeoxycholate solution under neutral conditions. The method was applied to the optical purity determination of trimetoquinol hydrochloride. The effects of surfactant concentrations and some additives to the micellar solution are briefly described.

Separation of the stereoisomers of an allenic E-type prostaglandin.

Enprostil (I) is a synthetic dehydro-prostaglandin E2 containing a chiral allene moiety which is unresolved relative to the four remaining chiral centers. The relative configuration of the four remaining chiral centers is consistent with that of the naturally occurring E series of prostaglandins. Thus, enprostil exists as enantiomeric pairs of two allenic epimers. An analytical procedure has been developed that separates the four optical isomers present in enprostil. This procedure involves, first, the acid-catalyzed dehydration of enprostil to its corresponding prostaglandin A analogue followed by derivatization with beta-naphthylsulfonyl-L-prolyl chloride. The resulting diastereomeric sulfonate esters are separated on an achiral silica gel high-performance liquid chromatographic column. This procedure has been applied to the analysis of both enprostil drug substance and enprostil formulated in a propylene carbonate solution from soft elastic gelatin capsules. An efficient procedure for the recovery of enprostil from the solution formulation is also described.