Holly J. Perpall

Separation of Organophosphonates by Ion Chromatography with Indirect Photometric Detection

Abstract An ion chromatographic method which utilizes lithium trimesate to separate three diphosphonate drugs and two process related organophosphonates is described. The lack of a chromophore on the five species and the high absorptivity of the trimesate anion at 254 nm allows for facile detection using indirect photometry. The effects of mobile phase concentration on the capacity factor of the species were investigated and a logarithmic relationship was established which was found to be dependent on the charge of the analyte anion and the mobile phase anion.

Chromatographic Analysis of Residual Acetate in Bulk Drugs

Abstract An ion chromatographic method for the determination of the residual acetate in hulk drug was developed. The drug was MK0476, an LTD4 antagonist. The compound also has a carboxyl functionality, which would interfere with the detection of the acetate ion. A solid phase extraction through a Sep-Pak cartridge was pursued for the removal of MK0476 from the matrix. Since the analyte does not have a chromophore, a mobile phase containing trimesic acid facilitated its detection by indirect photometric detection. The separation was performed on a polymeric strong union exchange column. The influence of pH, concentration of trimesic acid, and temperature were studied. Chloride ion was found to be a contaminant that was interfering in the analysis. To improve the separation between chloride and acetate ions, methanol was added to the mobile phase, leading to complete separation between the two species. Recovery of the acetate ion was determined as 92.3%. The method was applied to real samples with good resu...

Flow injection determination of Triton X-100 with on-line solid-phase extraction

A simple and rapid method for the determination of Triton X-100 in the presence of a quinoline derivative is described. The method involves flow injection with on-line cation-exchange solid-phase extraction. The carrier consists of a mixture of 5 mmol dm–3 aqueous KH2PO4(pH 2.0) and isobutyl alcohol–acetonitrile (50 + 50, v/v) in the proportion 65 + 35, v/v. Under these conditions, Triton X-100 elutes unretained, while the quinoline derivatives are retained on the extractor. Authentic samples were analysed by this method, with good precision and reproducibility.

Drug substance manufacture process control: application of flow injection analysis and HPLC for monitoring an enantiospecific synthesis

Effective process control can only be achieved through an understanding of the operating issues of the reaction. The development and use of effective and rugged analytical methods is necessary to monitor these parameters. The intent of this paper is to present some key analytical issues encountered in the synthesis of MK-0679, an LTD4 antagonist. In a key step of the compounds synthesis, a prochiral diester intermediate undergoes an enantioselective enzymatic hydrolysis (in the presence of Triton X-100) leading to the (S)-ester acid. Subsequent processing transforms the ester acid into the final product. The residual amount of the detergent in the final product, the rapid determination of the enzymatic activity and the optical purity of the final product emerged as key issues in the control of the reaction. As a solution, two techniques were utilized and are presented: flow injection analysis and HPLC.

Validation of a Separation of Diastereomers in the Pharmaceutical Industry

Abstract Method validation is an important step in any method development and has important implications in the pharmaceutical industry. Particular efforts should be directed towards the reproducibility, sensitivity and ruggedness of each method developed. In this paper, we report the validation of an HPLC method for the separation of the L-699, 392 and its (S, R) diastereomer. This compound contains two chiral centers and a carboxyl functionality able to participate in a hydrogen bonding process. In order to obtain maximum sensitivity, the elution order of the two diastereomers was adjusted such that the minor diastereomer eluted before the major one. To achieve this elution order a nonpolar mobile phase consisting of methylene chloride and n-propanol containing quinine as a hydrogen bond acceptor was used. In order to optimize the separation, the influence of quinine concentration on the capacity and separation factor of the two diastereomers, influence of the polar modifier in the mobile phase and infl...

Micellar enhanced cyanide ion determination in samples from synthetic organic processes

A method was developed for the recovery and determination of cyanide ion in organic sample matrices. To facilitate the solubilization of cyanide ions, cetyltrimethylammonium bromide (CTAB) was added at concentrations above the critical micelle concentration. Sample cyanation reaction products consisted of solvent mixtures of a hydroxynitrile in DMF-toluene or DMF-isopropylacetate (IPAC). Spectrophotometric determination of cyanide ion at 578 nm by the pyridine-barbituric acid method was automated by flow injection analysis. Recovery of cyanide ion from spiked samples was 93.2% in DMF-IPAC solvent matrix and 93.9% in DMF-toluene. Low alkali concentration was observed to favor solubilization of cyanide ion in the micellar solution.

Quantitative Analysis of a Chloroquinolin-Ethenyl Phenyl Derivative Using Thin Layers Impregnated With Di-P-Toluyl Tartaricacid

Abstract Thin Layer Chromatography (TLC) is an established method for the evaluation of final product drug and intermediate impurity profiles. Quantitative TLC has gained credibility within the Pharmaceutical industry as a result of the latest developments in an availability of scanning technology. In the present paper we wish to report a quantitative TLC method for the determination of some potential impurities which may exist in a final bulk drug MK0679. In order to improve the selectivity of the chromatographic method, di-p-toluyl tartaric acid was impregnated on the stationary phase. Utilizing the modified layer, complete separation of the known impurity was obtained. The calibration curves for all components studied were linear and the detection limits obtained were less than 5ng.

Determination of Vinylmagnesium Halide Reagents by High-performance Liquid Chromatography After Reaction With Anthraldehyde

A reversed-phase HPLC method has been developed for the determination of vinylmagnesium chloride and vinylmagnesium bromide, based on the assay of 1-(9-anthryl)propen-2-ol, the product in the reaction between a vinylmagnesium halide and 9-anthraldehyde. The HPLC system with UV detection and an acetonitrile–water mobile phase containing phosphoric acid buffer was used for the separation and quantification of the reaction product after extraction. The method is selective for 1-(9-anthryl)propen-2-ol and linear response was established at 227 nm in the 0.002 to 0.5 mg ml–1 concentration range. Vinylmagnesium halide concentration was calculated by using benzophenone as an external reference standard to standardize the response of authentic 1-(9-anthryl)propen-2-ol.