Simultaneous Determination of Cardenolides by Sonic Spray Ionization Liquid Chromatography-Ion Trap Mass Spectrometry—A Fatal case of Oleander Poisoning*

Arao, Tomonori; Fuke, Chiaki; Takaesu, Hajime; Nakamoto, Masakazu; Morinaga, Yasumasa; Miyazaki, Tetsuji

doi:10.1093/jat/26.4.222

Cited by 34 publications

(22 citation statements)

References 10 publications

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“…In contrast, the study of Wang et al [16] reported an oleandrin plasma concentration of 7 ng/ml for a volunteer 3 h after an intramuscular dose of 15 mg oleander extract for cancer treatment. This value is remarkably high compared to this case as well as other case reports [15,17], and can be explained only by an acquired tolerance of the volunteer.…”

Section: Resultssupporting

confidence: 57%

“…For example, in two cases of oleander poisoning in adults, comparable digoxin levels of 1.2 [8] and 1.5 ng/ml [9], respectively, in the blood samples were obtained; in these cases the immunoassays used yielded completely different results-mild cardiac symptoms [8] and death [9]. In contrast, well-defined toxicological data were published by Tracqui et al [15], who reported 1.1 ng/ml oleandrin (venous blood) in a non-fatal case that resulted in mild cardiac symptomatology, and by Arao et al [17], who reported 9.8 ng/ml oleandrin (heart blood) in a fatal poisoning.…”

Section: Resultsmentioning

confidence: 98%

“…These include immunoassays using chemiluminescent (ACS), radio labelling (RIA), and fluorescence polarisation (FPIA) as detection system [5][6][7][8][9], as well as thin layer chromatography (TLC) [10,11] and high-performance liquid chromatography (HPLC) combined with derivatisation and fluorescence detection (FLD) [12,13] and with mass spectrometry (MS) [14][15][16][17], a very sensitive and specific method for the analysis of plant toxins [18,19].…”

Section: Introductionmentioning

confidence: 99%

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A non-fatal oleander poisoning

et al. 2005

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The study presents a case of non-fatal poisoning with oleander blooms in a 47-year-old female, with emphasis on the importance of toxicological service in a clinical emergency. After repeated vomiting at home, the patient was admitted at the hospital with cardiac symptoms more than 18 h after the ingestion. Serum samples were assayed immunochemically for digitoxin-related compounds by electrochemiluminescent immunoassay, and using HPLC/MS/MS analysis for oleandrin, the main cardiac glycoside of Nerium oleander. Confirming the non-specific immunoassay results, which are often clinically over-interpreted, oleandrin was detected by HPLC/MS/MS in the serum sample in a concentration of 1.6 ng/ml upon admission. Comparison with previous reports indicates that single compound analysis only permits a toxicological assessment for oleander poisoning and results in the proposal to classify an oleandrin level between 1.0 and 2.0 ng/ml as toxic blood plasma/serum concentration.

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Section: Resultssupporting

confidence: 57%

Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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A non-fatal oleander poisoning

et al. 2005

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“…other proposed improvements in the ionization technique were the sonic spray devices and the introduction of APPI [20,[61][62][63][64][65]. The latter interface showed its usefulness in the analysis of rather nonpolar steroidal molecules.…”

Section: Purity Analysis and Impurity Profilingmentioning

confidence: 99%

MS Applications in Support of Medicinal Chemistry Sciences

Honing¹,

Ingelse²,

Pramanik³

2013

Mass Spectrometry for Drug Discovery and Drug Development

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In the drug discovery process, medicinal chemistry plays a crucial role in the optimal design and synthesis (production) of new chemical entities (NCEs) or new biological entities (NBEs); this is true for a single entity as well as a complete compound library. A key requirement in this field of science is the optimization of both the chemical and the biological properties of these potential drug-like compounds. Important criteria are the design of efficient synthesis routes, the balancing of the physical chemical properties with optimal in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) processes, and a profound understanding of the pharmacodynamics in the appropriate pharmacological models. In the lead optimization stage, an important step is scaling up the synthesis route as needed for the execution of toxicology studies and the screening of suitable drug formulations. In summary, medicinal chemistry support includes participating in a large variety of activities and decision making processes that play a key role in the search for either a "first in class" new drug or a "best in class" new drug [1].These "drug discovery" processes are continuously under pressure, as the research and development (R&D) costs continue to increase and more data are requested before new drug candidates are taken into (pre-)clinical development. Hence, the choice of "targeted" high-throughput screening (HTS) libraries, the process of hit appraisal, and the understanding of target-ligand interactions can be considered the starting points for a new drug discovery program [2]. Next, the main focus is on the discovery of a lead compound; typically, this is a compound showing promising data regarding target affinity, reasonable efficacy in cellular models, good physical chemical parameters (i.e., a "drug-like" compound), and acceptable oral bioavailability in Mass Spectrometry for Drug Discovery and Drug Development, First Edition. Edited by Walter A. Korfmacher.

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“…Recently, very sensitive and specific LC-MS/MS methods for the identification and quantification of digoxin and some related cardiac glycosides like oleandrin in biological matrices have been described [5][6][7][8]13]. Compared to immunoassay methods, LC-MS/MS methods are valuable for the confirmation of oleander intoxication in human and animal clinical cases in which immunoassays for digoxin or digitoxin are used as screening tools, especially if such cases involve forensic investigations.…”

Section: Introductionmentioning

confidence: 99%