The successful development of a catalytic imine asymmetric hydrogenation process for the reduction of the hydrochloride salt of 1-phenyl-3,4-dihydroisoquinoline to 1-(S)-phenyl-1,2,3,4-tetrahydroisoquinoline is described. This represents a novel approach to the key intermediate in preparing the urinary antispasmodic drug solifenacin, (1S)-(3R)-1-azabicyclo[2.2.2]oct-3-yl-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate. Suitable reaction conditions were identified through an extensive screen of catalysts and combination of solvents and additives. The best reaction conditions: [Ir(COD)Cl]2-(S)-P-Phos, molar substrate to catalyst ratio (S/C) of >1000/1, THF, 1–2 equiv of H3PO4, 60 °C, 20 bar H2, were reproduced on a 200 g scale (95% isolated yield, 98% ee and >99% HPLC product purity).

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SummaryA reversed-phase HPLC method for the analysis of cephalexin (74 (aminophenylacetyl)amino]-3-methyl-8-oxo-S-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid) by isocratic separation is described. A comparison is made between the ultrafiltration and the extraction procedure developed in our laboratory. The extraction procedure, based on the deproteinization of plasma with perchloric acid followed by the extraction with dichloroethane and separation of cephalexin on a reversed phase column, gave better recovery. Quantitative validation of our method has been performed by an external standard technique. The relative standard deviations were between 1.1 and 1.9% in the within-day assay and between 1.2 and 2.2% in the inter-day assay. The limit of detection was 0.14 kg/ml and the limit of quantification was 0.28 kg/ml. This method is rapid, sensitive, simple, and reproducible. The LC MS/MS technique was successfully used for identification and quantification of cephalexin in human plasma samples.

SummaryThe quantitative CE analysis of fluorine and monofluorophosDhate in toothpastes is described. Separation is performed hexane as internal standard), separated on a DC 200 packed column, and detected bv flame ionization (FID).using a Waters CIA-Pak chemistry kit with Waters Electro Osmotic Flow Modifiers on a CE instrument from Spectra Physics (Spectra-phoresis 500) at elevated temperatures up to 40°C and at a low temperature of 10"C.The quantitative results and the simplicity are compared for the CE method, the existing standard GC procedure described in the Official Journal of the European Communities, and the procedure employing a fluoride-ion-specific electrode.

We investigated a column with varying physical properties. A change in velocity was induced by a continuously varying the diameter inside the column. Analytical dimensions of the column were used. The diameter was continuously reduced from the analytical one (4.0 mm) to a diameter typical for narrow-bore columns (2.5 mm). Our interest was focused on the efficiency of a conical column and on the mobile phase velocity in it. The results obtained with the conical column were compared to those obtained with the conventional analytical column and the narrow column. The diameter of the narrow column (3.3 mm) was the same as the average diameter of the conical column. The advantage of the conical column over the narrow column was the greater loadability of the conical column and better dynamic efficiency. Compared to the conventional analytical column, a higher linear velocity at the same flow rate was achieved. Therefore, the retention times were shorter and consumption of the mobile phase was smaller.