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Biomedical subjects

D J Burinsky

Publications and source records attributed to D J Burinsky.

8 recordsLinked to original sources
PubMed2001

Isolation of the components of a complex mixture by means of column switching for their enhanced detection by mass spectrometry.

Mass spectral characterization of low-level impurities in drug substances and formulations may be challenging when using a validated HPLC method developed for optimal chromatographic performance. In many cases, either the mobile phase contains non-volatile additives that are deleterious to the operation of the mass spectrometer, or some of the related substances fail to ionize effectively under electrospray ionization or atmospheric pressure chemical ionization conditions. This paper describes a way to capture these low-level compounds from an analytical HPLC column using a small trapping column. Mixture components are retained on the trapping column by means of reducing the solvent strength of the eluent. Subsequent elution of trapped compounds using mobile phases more amenable to mass spectral analysis yields improved detection and characterization of low-level compounds of interest. Possible applications of peak trapping and elution include: (1) analysis of compounds separated using a mobile phase containing high concentrations of non-volatile additives, (2) analysis of organic acids separated using a low-pH mobile phase (containing trifluoroacetic acid), and (3) improving the detection limit of a low-level compound of interest through multiple collections. The peak trapping apparatus and optimization experiments are described.

Chromatography, High Pressure Liquid↗
PubMed2001

Automated molecular weight assignment of electrospray ionization mass spectra.

Process improvements in the synthesis of therapeutic agents and their intermediates are often facilitated by identification of reaction by-products. Analysis by liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization is a powerful approach for obtaining molecular weight information for these compounds. Such analyses are well suited for 'open-access' mass spectrometry using generic chromatographic conditions, provided spectral interpretation for unknown compounds is facile. We have developed a software application (MassAssign) that facilitates automated data processing and molecular weight assignment for chromatographic peaks detected by any standard ultraviolet-visible wavelength detector. The program assigns [M + H](+) ions (and thus molecular weight) in the mass spectra using predetermined criteria. This evaluation process differentiates [M + H](+) ions from other signals in a complex mass spectrum such as those resulting from chromatographic coelution or the presence of multiple species (i.e., fragment ions, singly charged ions, doubly charged ions, adduct ions, proton-bound dimers, etc.). Once the program has evaluated all ions in a mass spectrum that exceed a preset abundance threshold, MassAssign reports either a numeric value-indicating the chromatographic peak consists of a single component having the displayed molecular weight, 'MC'-indicating the peak consisted of multiple components, or 'ND'-that a molecular weight could not be determined unequivocally. The performance of the program was evaluated by comparing mass assignments made by MassAssign against manual interpretation for 55 samples analyzed by positive electrospray ionization using a generic HPLC method. Correct molecular weight assignments were obtained in 90% of the cases.

Algorithms↗
PubMed2001

Identification of a pharmaceutical packaging off-odor using solid phase microextraction gas chromatography/mass spectrometry.

The use of a solid phase microextraction (SPME) sampling technique, in conjunction with gas chromatography/mass spectrometry (GC/MS) analysis, to identify an off-odor in a heat-stressed pharmaceutical packaging material is described. The ability of the commercially available polydimethylsiloxane (PDMS) coated microfiber to concentrate a trace volatile compound of interest enabled identification of the odor compound of interest. Despite being present at levels that defied detection using conventional headspace sampling techniques, ethyl-2-mercaptoacetate was determined to be the compound responsible for the offending odor. Formation of the thioester resulted from an unanticipated reaction (either esterification or transesterification) between a common residual solvent (ethanol), present in a commonly used pharmaceutical tablet dispersant, and low-level amounts of reactants or synthetic intermediates of an FDA-approved polyvinyl chloride (PVC)-resin thermal stabilizing agent.

Drug Packaging↗
PubMed2001

Mass spectral fragmentation reactions of a therapeutic 4-azasteroid and related compounds.

Mass spectra were acquired for a therapeutic 4-azasteroid (dutasteride), and some related compounds, using various ionization conditions (EI, CI, APCI and ESI) in both positive and negative ion modes. The ionization and fragmentation behavior of the compound dutasteride, its precursors and several analogs is reported. Positive atmospheric pressure chemical ionization (APCI+) and positive electrospray ionization (ESI+) produced distinctive collision-induced dissociation (CID) spectra for the respective [MH]+ ions of dutasteride. The spectral differences are attributed to ion populations having either different structures or different internal energy distributions (as a consequence of the method of ionization). Irrespective of their origin, the protonated molecules undergo interesting fragmentation reactions when collisionally activated. The identity of the major fragmentation products was confirmed by accurate mass measurement. The negative APCI mass spectrum of dutasteride displays extensive dehydrohalogenation, apparently due to the thermal component of the APCI process. Some of the resulting radical anions display remarkable stability toward collisional decomposition. Details of the fragmentation behavior for the negative ion species and their relationship to the positive ion results are discussed.

5-alpha Reductase Inhibitors↗
PubMed1996

Characterization of tepoxalin and its related compounds by high-performance liquid chromatography/mass spectrometry.

High-performance liquid chromatography/mass spectrometry (HPLC/MS) was used to identify and elucidate key structural characteristics of a novel dual cyclooxygenase/lipoxygenase inhibitor, tepoxalin (3-[5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-pyrazolyl]-N-hydroxy- N-methylpropanamide), its synthesis-related byproducts in bulk drug substance, and degradation products stemming from probe stability studies. Such information is needed to assist in synthesis optimization and in the preparation of stable formulations for toxicity studies and clinical trials. High-performance liquid chromatography, in conjunction with mass spectrometry (HPLC/MS) and UV photodiode array detection, can often expedite the gathering of preliminary data that contribute to several aspects of the pharmaceutical development process.

Chromatography, High Pressure Liquid↗
PubMed1994

Characterization of cladribine and its related compounds by high-performance liquid chromatography/mass spectrometry.

High-performance liquid chromatography/mass spectrometer (HPLC/MS) was used to identify and structurally characterize the modified nucleoside cladribine (2-chloro-2'-deoxy-beta-adenosine) and 13 synthesis-related byproducts in bulk drug. Confirmation of compound identity was accomplished by spectral analysis (1H and 13C NMR spectroscopy, mass spectrometry, and UV absorption spectroscopy) of the related compounds as isolated from crude mixtures of the drug substance and by spiking experiments with authentic standards. The use of on-line mass spectrometric analysis (i.e., LC/MS) to augment UV absorption spectra permitted rapid identification of many of the compounds of interest.

Chromatography, High Pressure Liquid↗
PubMed1992

Characterization of a synthetic peptide impurity by fast-atom bombardment-tandem mass spectrometry and gas chromatography-mass spectrometry.

Fast-atom bombardment-tandem mass spectrometry (FAB-MS-MS) was used to characterize the structure of atosiban, a synthetic oxytocin antagonist, and one of its synthesis-related impurities. The nature of the structural modification in the impurity of interest, replacement of the proline residue by 5-aminovaleric acid, was determined directly from its product ion MS-MS spectrum. Confirmation of the identity of the impurity was accomplished with GC-MS.

Amino Acids↗