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Advanced Analysis of Compounds of To...

Dzisam, Joseph K.

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Advanced Analysis of Compounds of Toxicological Importance by Ice Concentration Linked with Extractive Stirrer (ICECLES) GC-MS and RP-HPLC-ESI-MS-MS.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Advanced Analysis of Compounds of Toxicological Importance by Ice Concentration Linked with Extractive Stirrer (ICECLES) GC-MS and RP-HPLC-ESI-MS-MS./
作者:	Dzisam, Joseph K.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	138 p.
附註:	Source: Dissertation Abstracts International, Volume: 80-09(E), Section: B.
Contained By:	Dissertation Abstracts International80-09B(E).
標題:	Chemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13811757
ISBN:	9781392118740

Advanced Analysis of Compounds of Toxicological Importance by Ice Concentration Linked with Extractive Stirrer (ICECLES) GC-MS and RP-HPLC-ESI-MS-MS.
Dzisam, Joseph K.

Advanced Analysis of Compounds of Toxicological Importance by Ice Concentration Linked with Extractive Stirrer (ICECLES) GC-MS and RP-HPLC-ESI-MS-MS. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 138 p.

Source: Dissertation Abstracts International, Volume: 80-09(E), Section: B.

Thesis (Ph.D.)--South Dakota State University, 2019.

Cyanide and nitrosoamines (NAs) are ubiquitous compounds, found in our food and water, either by natural process or through man-made activities. The toxicity of cyanide is exerted by its ability to inhibit metalloenzymes such as cytochrome c oxidase, causing concomitant cascades of biochemical effects such as lactic acidosis, inhibition of ATP production, respiratory seizure, and potential death. Nitrosoamines, on the other hand, undergo biotransformation (metabolic activation in cytochrome P450) in the body to produce unstable intermediates that alkylate DNA, causing mutations, and leading to carcinogenesis. In order to further the advancement of a promising cyanide, cobinamide (Cbi), an LC-MS-MS method was developed to analyze cyanide-complex Cbi, while an ICECLES-GC-EI-MS procedure was developed to detect nitrosodipropylamine (NDPA) at low concentrations in drinking water via a flexible, facile, relative easy performed, and green method.

ISBN: 9781392118740Subjects--Topical Terms:

516420
Chemistry.

Advanced Analysis of Compounds of Toxicological Importance by Ice Concentration Linked with Extractive Stirrer (ICECLES) GC-MS and RP-HPLC-ESI-MS-MS.
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245 1 0 $a Advanced Analysis of Compounds of Toxicological Importance by Ice Concentration Linked with Extractive Stirrer (ICECLES) GC-MS and RP-HPLC-ESI-MS-MS.
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500 $a Source: Dissertation Abstracts International, Volume: 80-09(E), Section: B.
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520 $a Cyanide and nitrosoamines (NAs) are ubiquitous compounds, found in our food and water, either by natural process or through man-made activities. The toxicity of cyanide is exerted by its ability to inhibit metalloenzymes such as cytochrome c oxidase, causing concomitant cascades of biochemical effects such as lactic acidosis, inhibition of ATP production, respiratory seizure, and potential death. Nitrosoamines, on the other hand, undergo biotransformation (metabolic activation in cytochrome P450) in the body to produce unstable intermediates that alkylate DNA, causing mutations, and leading to carcinogenesis. In order to further the advancement of a promising cyanide, cobinamide (Cbi), an LC-MS-MS method was developed to analyze cyanide-complex Cbi, while an ICECLES-GC-EI-MS procedure was developed to detect nitrosodipropylamine (NDPA) at low concentrations in drinking water via a flexible, facile, relative easy performed, and green method.
520 $a Cbi has shown promise as a therapeutic for cyanide poisoning. While current analysis techniques only measure total Cbi, methods to elucidate the behavior of cyanide-bound Cbi, total Cbi, and available Cbi (i.e., the difference between cyanoCbi and total Cbi) would be valuable for biomedical and pharmacokinetic studies. Therefore, a method was developed for the analysis of cyanoCbi in plasma via liquid chromatography-tandem mass spectrometry (LC-MS-MS). Plasma samples were prepared by denaturing proteins with 10% ammonium hydroxide in acetonitrile. The resulting mixture was centrifuged, and the supernatant was removed, dried, and reconstituted. CyanoCbi was then analyzed via LC-MS-MS. The limit of detection was 0.2 microM, and the linear range was between 1-200 microM. The accuracy was 100+/-17% and the precision, measured by relative standard deviation (%RSD), was ≤18.5%. Carryover, a severe problem when analyzing Cbi via liquid chromatography, was eliminated using a polymeric-based stationary phase (PLRP-S) and a controlled washing protocol. The method allowed evaluation of the cyanide-bound and 'available' Cbi from treated animals and, when paired with a method for total Cbi analysis. This method allowed for estimation of Cbi utilization when treating cyanide poisoning and verified for the first time, the hypothesized mechanism of treatment of cyanide poisoning by Cbi (direct binding of cyanide).
520 $a To overcome the challenges associated with the analysis of NAs at ultratrace levels (i.e., difficult extraction protocols, laborious sample preparation techniques, and requirement for sophisticated/expensive instrumentation), an advanced sample preparation technique, ICE Concentration Linked with Extractive Stirrer (ICECLES), coupled to an inexpensive low-resolution gas-chromatography electron ionization mass-spectrometry instrument was used to analyze NDPA (MRL = 7 ng/L (ppt)). An LOD of 0.2 ng/L was obtained for NDPA, along with linear range of 2 to 50 ng/L was produced (using NDPA-d14 internal standard). Both inter- and intraassay precision were ≤13%RSD, while the method accuracy was 100+/-17.5%. The ICECLES method was applied to screen for possible NA contamination in selected drinking water sources. The concentration of NDPA in one drinking water source was 2.38+/-0.34 ng/L. Moreover, NDPA was detected in the two other municipalities tested (i.e., concentrations > 0.2 ng/L), but it was not quantifiable.
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