Unknown Impurity (unknown + impurity)

Distribution by Scientific Domains

Selected Abstracts

Influence of differently ionized species on fragmentation pathways and energetics of a potential adenosine receptor antagonist using a triple quadrupole and a multistage LTQ-OrbitrapÔ FTMS instrument

Wendy Zhong
A systematic study was conducted to investigate the influence of differently ionized species on the fragmentation pathways and energetics of a piperazine-containing adenosine by using different cations or anions. Very different fragmentation mechanisms were observed in protonated- versus sodiated-molecules, which indicated that the proton is mobilized to promote the charge-direct fragmentation, whereas Na+ cation was fixed at the heterotricyclic ring structure provoking charge-remote fragment ions. This finding was also supported by the results observed in the fragmentation behaviors in the deprotonated-molecule. The energetics of these fragment ions were also explored by using the breakdown curves obtained from the triple quadrupole and LTQ-OrbitrapÔ instrument. The data indicated that the lowest energy pathways in the protonated-molecule [M+H]+ involve breaking a CN bond connecting an ethylene bridge and heterotricyclic ring structure. The lowest energy pathway is the cleavage of a CO bond connecting the methoxy ethyl group and phenolic oxygen to form a distonic radical ion for a sodiated-molecule [M+Na+]and a deprotonated-molecule [M-H],. The data suggest that by choosing the differently ionized species, one can probe different fragmentation channels that can provide additional structure information for an unknown impurity and possibly degradation product identification. In addition, by comparing the data obtained from triple quadrupole and LTQ-Orbitrap instruments, one can develop further understanding of the differences in the fragmentation behaviors due to the variations in the collision activation-dissociation process. From the side-by-side comparison with the breakdown curves obtained for both instruments, the difference in fragmentation behaviors caused by the difference in dissociation processes that occur in these two types of instruments can be probed. J. Heterocyclic Chem., (2009). [source]

Pharmaceutical impurity identification: A case study using a multidisciplinary approach

Karen M. Alsante
Abstract A multidisciplinary team approach to identify pharmaceutical impurities is presented in this article. It includes a representative example of the methodology. The first step is to analyze the sample by LC-MS. If the structure of the unknown impurity cannot be conclusively determined by LC-MS, LC-NMR is employed. If the sample is unsuitable for LC-NMR, the impurity needs to be isolated for conventional NMR characterization. Although the technique of choice for isolation is preparative HPLC, enrichment is often necessary to improve preparative efficiency. One such technique is solid-phase extraction. For complete verification, synthesis may be necessary to compare spectroscopic characteristics to those observed in the original sample. Although not widely practiced, an effective means of getting valuable structural information is to conduct a degradation study on the purified impurity itself. This systematic strategy was successfully applied to the identification of an impurity in the active pharmaceutical ingredient 1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(1-hydroxy-1-methyl-ethyl)-furan-2-sulphonylurea. Identification required the use of all of the previously mentioned techniques. The instability of the impurity under acidic chromatographic conditions presented an additional challenge to purification and identification. However, we turned this acidic instability to an advantage, conducting a degradation study of the impurity, which provided extensive and useful information about its structure. The following discussion describes how the information gained from each analytical technique was brought together in a complementary fashion to elucidate a final structure. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2296,2309, 2004 [source]

Investigation of Catalytic Chain Transfer Copolymerization of Methacrylates

Anatoly N. Nikitin
Abstract Batch experiments were carried out to investigate the kinetics of catalytic chain transfer copolymerization of methyl methacrylate and n -butyl methacrylate. The Predici® model developed to represent the system describes the numerous experimental data measured at high concentrations of Co(II) catalyst, taking into account the chain-length dependencies of termination, propagation and catalytic chain transfer. The constants for catalytic chain transfer are determined as 2.3,×,104 for both methyl methacrylate and n -butyl methacrylate from fitting the experimental data. Two inhibition mechanisms are shown to describe the decrease of the polymerization rate in the presence of catalyst equally well, with an unknown impurity dissolved in initiator introduced to explain experimental profiles measured at high initiator concentrations. [source]

Drug impurity profiling by capillary electrophoresis/mass spectrometry using various ionization techniques

Paul Hommerson
Capillary electrophoresis/mass spectrometry (CE/MS) is predominantly carried out using electrospray ionization (ESI). Recently, atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) have become available for CE/MS. With the VUV lamp turned off, the APPI source may also be used for CE/MS by thermospray ionization (TSI). In the present study the suitability of ESI, APCI, APPI and TSI for drug impurity profiling by CE/MS in the positive ion mode is evaluated. The drugs carbachol, lidocaine and proguanil and their potential impurities were used as test compounds, representing different molecular polarities. A background electrolyte of 100,mM acetic acid (pH 4.5) provided baseline separation of nearly all impurities from the respective drugs. APPI yielded both even- and odd-electron ions, whereas the other ionization techniques produced even-electron ions only. In-source fragmentation was more pronounced with APCI and APPI than with ESI and TSI, which was most obvious for proguanil and its impurities. In general, ESI and TSI appeared the most efficient ionization techniques for impurities that are charged in solution achieving detection limits of 100,ng/mL (full-scan mode). APPI and APCI showed a lower efficiency, but allowed ionization of low and high polarity analytes, although quaternary ammonium compounds (e.g. carbachol) could not be detected. Largely neutral compounds, such as the lidocaine impurity 2,6-dimethylaniline, could not be detected by TSI, and yielded similar detection limits (500,ng/mL) for ESI, APPI and APCI. In many cases, impurity detection at the 0.1% (w/w) level was possible when 1,mg/mL of parent drug was injected with at least one of the CE/MS systems. Overall, the tested CE/MS systems provide complementary information as illustrated by the detection and identification of an unknown impurity in carbachol. Copyright © 2009 John Wiley & Sons, Ltd. [source]