Simultaneous quantification of batrachotoxin and epibatidine in plasma by ultra-performance liquid chromatography/tandem mass spectrometry. 2017

Yosuke Shiraishi, and Tadashi Ogawa, and Takayoshi Suzuki, and Masae Iwai, and Maiko Kusano, and Kei Zaitsu, and Fumio Kondo, and Akira Ishii, and Hiroshi Seno
Department of Legal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan; Department of Pharmacy, Fujita Health University Hospital, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.

An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantification of batrachotoxin and epibatidine in plasma. Plasma samples were pretreated by liquid-liquid extraction with acetonitrile and methanol. The toxins were separated on a reversed phase C18-column (2.1mm×50mm, 1.7μm) using a formic acid/acetonitrile gradient elution. Quantification was carried out by mass chromatography with each product ion referenced against midazolam-d4 as an internal standard (IS). The two toxins and the IS were separated within 2min. The calibration curves for the two toxins spiked into human plasma showed good linearities in the range from 2.5 to 250ng/mL. The detection limits were estimated to be 0.5ng/mL for batrachotoxin and 1ng/mL for epibatidine with a signal-to-noise ratio of 3:1. Overall recoveries ranged from 69.6% to 98.2%, and no significant matrix effects were observed. The intra- and interday accuracies were 94.7-102.3%, and the precisions were 1.0-10.3%. This method was successfully applied for the quantification of batrachotoxin and epibatidine in rat plasma samples taken after intraperitoneal administration of the toxins. This is the first report to use UPLC-MS/MS to simultaneously quantify batrachotoxin and epibatidine in plasma samples.

UI MeSH Term Description Entries
D007564 Japan A country in eastern Asia, island chain between the North Pacific Ocean and the Sea of Japan, east of the Korean Peninsula. The capital is Tokyo. Bonin Islands
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001001 Anura An order of the class Amphibia, which includes several families of frogs and toads. They are characterized by well developed hind limbs adapted for jumping, fused head and trunk and webbed toes. The term "toad" is ambiguous and is properly applied only to the family Bufonidae. Bombina,Frogs and Toads,Salientia,Toad, Fire-Bellied,Toads and Frogs,Anuras,Fire-Bellied Toad,Fire-Bellied Toads,Salientias,Toad, Fire Bellied,Toads, Fire-Bellied
D001496 Batrachotoxins Batrachotoxin is the 20-alpha-bromobenzoate of batrachotoxin A; they are toxins from the venom of a small Colombian frog, Phyllobates aurotaenia, cause release of acetylcholine, destruction of synaptic vesicles and depolarization of nerve and muscle fibers. Batrachotoxin B
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D053719 Tandem Mass Spectrometry A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection. Mass Spectrometry-Mass Spectrometry,Mass Spectrometry Mass Spectrometry,Mass Spectrometry, Tandem
D018712 Analgesics, Non-Narcotic A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS. Non Opioid Analgesic,Non-Opioid Analgesic,Nonopioid Analgesic,Nonopioid Analgesics,Analgesics, Nonnarcotic,Analgesics, Nonopioid,Non-Opioid Analgesics,Analgesic, Non Opioid,Analgesic, Non-Opioid,Analgesic, Nonopioid,Analgesics, Non Narcotic,Analgesics, Non-Opioid,Non Opioid Analgesics,Non-Narcotic Analgesics,Nonnarcotic Analgesics,Opioid Analgesic, Non

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