P. Tway

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.

Use of subcritical fluid chromatography for the separation of enantiomers using packed cellulose based stationary phase

Investigations into the parameters affecting the enantiomeric separation of an intermediate in the synthesis of a drug targeted for cardiac arrhythmia is presented. The separation was achieved under subcritical fluid chromatography using CO2 modified with methanol and co-modifiers isopropyl amine and methylene chloride. The stationary phase was a cellulose based stationary phase manufactured under the trade name Chiracel OB. The results showed the addition of methylene chloride had a noticeable effect on resolution while the separation factor, α, remained constant. The co-modifier, isopropyl amine, did not considerably influence the resolution, or separation factor. Temperature studies were performed in order to establish the thermodynamic parameters of the interaction between the enantiomers and the stationary phase. Plots of In k′ vs. 1/T proved to be curved, while plots of In α vs. 1/T were linear.

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...

Reliability of factor analysis in the presence of random noise or outlying data

Abstract Hirsch, R.F., Wu, G.L. and Tway, P.C., 1987. Reliability of factor analysis in the presence of random noise or outlying data. Chemometrics and Intelligent Laboratory Systems , 1: 265–272. The influence of random and determinate error on abstract factor analysis is investigated. A Monte Carlo study of the effect of random error in data from NMR and GC-MS experiments indicates that the eigenvalue ratio test and Malinowskis indicator function are more accurate that the imbedded error function in determining the number of significant factors or components. Outliers affect the analysis, but the level of deviation of a single outlier can be considerably larger than the random experimental error in the data before the effect is significant.

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.

Development of Practical HPLC Methods for Analysis and Quality Assessment of the Novel Carbonic Anhydrase Inhibitor MK-0507 and the Acetamidosulfonamide Intermediate

Abstract MK-0507 (Dorzolamide HCl, (4S,6S)-4-Ethylamino-5,6-dihydro-6-methyl-4H-thieno-[2,3-b] thiopyran-2-sulfonamide 7,7-dioxide hydrochloride) is the first topically active, water-soluble, carbonic anhydrase inhibitor to be developed for the treatment of glaucoma and ocular hypertension. Dorzolamide HCl is an effective and well tolerated agent as monotherapy for patients who cannot tolerate ophthalmic beta-blockers, and for those who need add-on therapy to beta-blockers.1 The steps taken in the development and validation of a fast and rugged reverse-phase HPLC method for the analysis and quality assessment of MK-0507 drug substance and acetamidosulfonamide intermediate are described. Four columns were used during the development: Du Pont Zorbax C-18, Rainin Microsorb C-8, Perkin Elmer CR-C8 and YMC4. The last two columns showed excellent resolution, peak shape, and precision. The selected HPLC method for acetamidosulfonamide, using the Perkin Elmer CR-C8 column, was validated with respect to linearity,...

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...

High Performance Liquid Chromatographic Detection of Residual Formaldehyde in a Hepatitisa Vaccine by Use of Hydralazine

Abstract An assay was developed that is capable of detecting levels of residual formaldehyde in viral vaccine dosage formulations to 0.01 μg/inL. The assay employs incubation of dosage formulation suspensions with hydralazine hydrochloride under mildly acidic conditions and elevated temperatures. Formaldehyde present is derivitized to yield s-triazolo-[3,4-a]-phthalazine. Selectivity of the assay is enhanced by performing reverse phase HPLC after the reaction, and monitoring elution of the fluorescent product. The presence of insoluble aluminum hydroxide in dosage formulations does not affect formaldehyde recovery. The assay was used to determine formaldehyde levels in dosage formulations and in in-process samples of a newly developed Hepatitis A vaccine.

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.

High-performance liquid chromatographic separation of an HIV-1 reverse transcriptase inhibitor and its enantiomer.

This article describes the direct separation of an HIV-1 reverse transcriptase inhibitor and its enantiomer by HPLC on a silica-bonded polyacrylamide (ChiraSpher) column. The column selection was based on specific interactions between the individual enantiomers and the chiral stationary phase. The influence of some chromatographic conditions, such as concentration of the polar modifier in the mobile phase, column flow-rate and column temperature, on column performance was investigated. The separation was applied to the determination of the minor enantiomer in the bulk drug and as low as 0.3% of minor enantiomer was detectable.