生物样品中大田软海绵酸类毒素代谢规律及检测方法的研究进展

doi:10.3724/SP.J.1123.2019.10016

色谱 ›› 2020, Vol. 38 ›› Issue (6): 621-626.DOI: 10.3724/SP.J.1123.2019.10016

生物样品中大田软海绵酸类毒素代谢规律及检测方法的研究进展

吕莹¹^,², 周志刚³, 陈思²^,⁴^,^*(), 张小军²^,⁴

¹ 浙江海洋大学水产学院, 浙江舟山 316022
² 浙江省海洋水产研究所水产品加工与质量安全研究室, 浙江舟山 316021
³ 舟山市公安司法鉴定中心, 浙江舟山 316021
⁴ 浙江省海洋渔业资源可持续利用技术研究重点实验室, 农业部重点渔场渔业资源科学观测实验站, 浙江舟山 316021

收稿日期:2019-10-16 出版日期:2020-06-08 发布日期:2020-12-10
通讯作者: 陈思
作者简介:陈思.Tel:(0580)2299872, E-mail:sichen_ns@163.com
基金资助:
舟山市科技计划项目(2017C32073)

Progress on the metabolic rules and detection methods for okadaic acid related toxins in biological samples

Lü Ying¹^,², ZHOU Zhigang³, CHEN Si²^,⁴^,^*(), ZHANG Xiaojun²^,⁴

¹ School of Fisheries of Zhejiang Ocean University, Zhoushan 316022, China
² Laboratory of Aquatic Product Processing and Quality Safety, Marine Fisheries Research Institute of Zhejiang Province, Zhoushan 316021, China
³ Zhoushan Police Evidence Identification Center, Zhoushan 316021, China
⁴ Key Laboratory of Sustainable Utilization of Technology Research for Fisheries Resources of Zhejiang Province, Scientific Observing and Experimental Station of Fishery Resources for Key Fishing Grounds, Ministry of Agriculture, Zhoushan 316021, China

Received:2019-10-16 Online:2020-06-08 Published:2020-12-10
Contact: CHEN Si
Supported by:
Science and Technology Program of Zhoushan(2017C32073)

摘要/Abstract

摘要：

近年来，中国赤潮污染日趋严重，因此引发多起贝类毒素中毒事件，威胁消费者的食用安全。大田软海绵酸（okadaic acid，OA）及其衍生物鳍藻毒素（dinophysistoxins，DTXs）是分布最广、危害最大的一类腹泻性贝类毒，具有急性腹泻毒性及多种慢性毒性。建立生物体液样品中OA类毒素残留的检测方法对辅助诊断患者的中毒情况极为必要。文章简要介绍了OA类毒素的理化性质、中毒事件、毒理作用，并详细总结了生物样品中OA类毒素代谢规律及检测方法的研究进展。

关键词: 液相色谱-串联质谱, 体内代谢, 大田软海绵酸, 生物样品, 综述

Abstract:

In recent years, red tide pollution in China has become increasingly serious, leading to a number of shellfish poisoning cases, thereby posing a threat to human health and safety. Okadaic acid (OA) and its analogs (dinophysistoxins, DTXs) are the most widely distributed diarrhetic shellfish poisons, which result in acute diarrheal toxicity and various types of chronic toxicity. It is imperative to establish a method for determination of OA related toxin residues in biological fluid samples, so that accurate diagnosis of poisoning in patients is possible. The present paper briefly introduced the main physicochemical properties, poisoning incidents, toxicological effects for the toxins, also summarized recent progress on the metabolic rules and detection methods for OA related toxins in biological samples.

Key words: liquid chromatography-tandem mass spectrometry (LC-MS/MS), in vivo metabolism, okadaic acid (OA), biological samples, review

吕莹, 周志刚, 陈思, 张小军. 生物样品中大田软海绵酸类毒素代谢规律及检测方法的研究进展[J]. 色谱, 2020, 38(6): 621-626.

Lü Ying, ZHOU Zhigang, CHEN Si, ZHANG Xiaojun. Progress on the metabolic rules and detection methods for okadaic acid related toxins in biological samples[J]. Chinese Journal of Chromatography, 2020, 38(6): 621-626.

图/表 3

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Year	Location of outbreak	Patients involved	Frequency	Ref.
1961-1981	Netherlands	not mentioned	5	^{[4, 5]}
1970-2004	Chile	>1500	>4	^{[6, 7]}
1976-1982	Japan	>1300	>34	^[8]
1978-1981	Spain	>5000	>3	^[9]
1980-2011	USA	>3496	5	^{[9, 10]}
1984-2009	France	>12000	>13	^{[11, 12]}
1990-2002	Denmark	>800	>3	^[9]
1990-2011	Canada	78	2	^{[13, 14]}
1997-2019	UK	125	3	^[15-17]
1997-2000	Australia	123	3	^[18]
2000	Greece	120	1	^[19]
2002	Belgium	403	1	^[20]
2011	China	>200	1	^[21]
2019	Brazil	9	1	^[22]

Year	Location of outbreak	Patients involved	Frequency	Ref.
1961-1981	Netherlands	not mentioned	5	^{[4, 5]}
1970-2004	Chile	>1500	>4	^{[6, 7]}
1976-1982	Japan	>1300	>34	^[8]
1978-1981	Spain	>5000	>3	^[9]
1980-2011	USA	>3496	5	^{[9, 10]}
1984-2009	France	>12000	>13	^{[11, 12]}
1990-2002	Denmark	>800	>3	^[9]
1990-2011	Canada	78	2	^{[13, 14]}
1997-2019	UK	125	3	^[15-17]
1997-2000	Australia	123	3	^[18]
2000	Greece	120	1	^[19]
2002	Belgium	403	1	^[20]
2011	China	>200	1	^[21]
2019	Brazil	9	1	^[22]

Toxin classifica- tion	Analyte	Matrix	Extraction solvent	Purification method	Analytical column	Quantitative range/ (ng/mL)	LOD/ (ng/mL)	Ref.
TTX: tetrodotoxin; STX: saxitoxin; NEO: neosaxitoxin; DA: domoic acid; MC: microcystin; MeOH: methanol; ACN: acetonitrile; AA: acetic acid; SCX: strong citation exchange; CBA: carboxyl bonded amide; PCX: polymer citation exchange; PA: polyamide; WCX: weak citation exchange; CCX: carboxyl citation exchange; PAX: polymer anion exchange; -: not mentioned.
DSP	OA, DTX-1, DTX-2	urine	V_sample:V_MeOH=1:4	SPE (C18 cartridge)	Waters XBridge BEH C18 (150 mm×3 mm, 5 μm)	-	0.7, 0.5, 0.7	[40]
	OA, DTX-1	urine	V_sample:V_MeOH: V_10%_{trichloroacetic}_acid:V_ACN=10:4:1:5	none	Waters ACQUITY UPLC BEH C18 (100 mm×2.1 mm, 1.7 μm)	-	-	[34]
		blood	V_sample:V_75%_MeOH=1:4	none		-	-
		feces	m_sample:V_MeOH=1:4	none		-	-
TTX	TTX	urine, plasma	V_sample:V_2%_AA=1:4	SPE (C18 and HILIC cartridges)	Agilent Atlantics dC18 (150 mm×2.1 mm, 5 μm)	2.5-20, 2.5-500	0.13	[41]
	TTX	urine	V_sample:V_0.1%_AA=1:1	online SPE (SCX and C18 cartridges)	HALO Penta-HILIC (75 mm×3 mm, 2.7 μm)	2.80-249	0.3	[42]
	TTX	urine blood	V_sample:V_ACN=1:10 V_sample:V_ACN=1:10	SPE (amide cartridge) SPE (CBA cartridge)	Agilent Zorbax HILIC Plus (100 mm×2.1 mm, 3.5 μm)	1-25 0.5-200	0.5 0.25	[43]
	TTX	urine, blood	V_sample:V_H₂O: V_{IS(voglibose)}=1:1:4	SPE (PCX cartridge)	Agilent PC HILIC (150 mm×2 mm, 5 μm)	2-1200	0.32	[44]
PSP	STX, NEO	urine	V_sample:V_H₂O:V_MeOH: V_ACN=2:2:1:10	SPE (PA cartridge)	Waters ACQUITY UPLC BEH Amide (100 mm×2.1 mm, 1.7 μm)	0.5-99.2, 2.1-207	0.2, 1	[45]
	STX, NEO	urine	V_sample:V_IS(¹⁵N7-STX): V_phosphate_buffer=20:1:40	online SPE (WCX cartridge)	Waters Atlantis Silica HILIC (50 mm×1 mm, 2 μm)	-	4.8, 10.1	[46]
	NEO	urine	V_sample:V_phosphate_buffer=1:5	SPE (CCX cartridge)	Waters Atlantis Silica HILIC (50 mm×2.1 mm, 3 μm)	0.01-1	0.001	[47]
ASP	DA	urine	V_sample:V_MeOH=1:1	SPE (PAX cartridge)	Waters ACQUITY UPLC HSS T3 (100 mm×2.1 mm, 1.8 μm)	-	0.12	[48]
	DA	urine plasma	V_sample:V_MeOH:V_H₂O=1:49:50 V_sample:V_MeOH=1:2	none none	Phenomenex Synergi Hydro-RP (50 mm×2.0 mm, 2.5 μm)	0.31-16 7.8 -1000	- -	[49]
	DA	blood	V_sample:V_formic_acid:V_H₂O=50:1:50	SPE (HILIC cartridge)	Agilent Zorbax SB-C8 (50 mm×2.1 mm, 1.8 μm)	1.0-10.6	0.17	[50]
CTX	MC-LR, MC-RR, MC-LA,	urine	V_sample:V_H₂O=1:24	SPE (C18 cartridge)	Waters HSS T3 C18 (50 mm×3 mm, 1.8 μm)	0.5-20	0.05, 0.05, 0.13, 0.14, 0.13, 0.05	[51]
	MC-LF, MC-LW, MC-YR	plasma, serum	V_sample:V₁₀₀_nmol/L_ZnSO₄=1:5	SPE (C18 cartridge)		0.25-10	0.08, 0.08, 0.30, 0.30, 0.30, 0.08

Toxin classifica- tion	Analyte	Matrix	Extraction solvent	Purification method	Analytical column	Quantitative range/ (ng/mL)	LOD/ (ng/mL)	Ref.
TTX: tetrodotoxin; STX: saxitoxin; NEO: neosaxitoxin; DA: domoic acid; MC: microcystin; MeOH: methanol; ACN: acetonitrile; AA: acetic acid; SCX: strong citation exchange; CBA: carboxyl bonded amide; PCX: polymer citation exchange; PA: polyamide; WCX: weak citation exchange; CCX: carboxyl citation exchange; PAX: polymer anion exchange; -: not mentioned.
DSP	OA, DTX-1, DTX-2	urine	V_sample:V_MeOH=1:4	SPE (C18 cartridge)	Waters XBridge BEH C18 (150 mm×3 mm, 5 μm)	-	0.7, 0.5, 0.7	[40]
	OA, DTX-1	urine	V_sample:V_MeOH: V_10%_{trichloroacetic}_acid:V_ACN=10:4:1:5	none	Waters ACQUITY UPLC BEH C18 (100 mm×2.1 mm, 1.7 μm)	-	-	[34]
		blood	V_sample:V_75%_MeOH=1:4	none		-	-
		feces	m_sample:V_MeOH=1:4	none		-	-
TTX	TTX	urine, plasma	V_sample:V_2%_AA=1:4	SPE (C18 and HILIC cartridges)	Agilent Atlantics dC18 (150 mm×2.1 mm, 5 μm)	2.5-20, 2.5-500	0.13	[41]
	TTX	urine	V_sample:V_0.1%_AA=1:1	online SPE (SCX and C18 cartridges)	HALO Penta-HILIC (75 mm×3 mm, 2.7 μm)	2.80-249	0.3	[42]
	TTX	urine blood	V_sample:V_ACN=1:10 V_sample:V_ACN=1:10	SPE (amide cartridge) SPE (CBA cartridge)	Agilent Zorbax HILIC Plus (100 mm×2.1 mm, 3.5 μm)	1-25 0.5-200	0.5 0.25	[43]
	TTX	urine, blood	V_sample:V_H₂O: V_{IS(voglibose)}=1:1:4	SPE (PCX cartridge)	Agilent PC HILIC (150 mm×2 mm, 5 μm)	2-1200	0.32	[44]
PSP	STX, NEO	urine	V_sample:V_H₂O:V_MeOH: V_ACN=2:2:1:10	SPE (PA cartridge)	Waters ACQUITY UPLC BEH Amide (100 mm×2.1 mm, 1.7 μm)	0.5-99.2, 2.1-207	0.2, 1	[45]
	STX, NEO	urine	V_sample:V_IS(¹⁵N7-STX): V_phosphate_buffer=20:1:40	online SPE (WCX cartridge)	Waters Atlantis Silica HILIC (50 mm×1 mm, 2 μm)	-	4.8, 10.1	[46]
	NEO	urine	V_sample:V_phosphate_buffer=1:5	SPE (CCX cartridge)	Waters Atlantis Silica HILIC (50 mm×2.1 mm, 3 μm)	0.01-1	0.001	[47]
ASP	DA	urine	V_sample:V_MeOH=1:1	SPE (PAX cartridge)	Waters ACQUITY UPLC HSS T3 (100 mm×2.1 mm, 1.8 μm)	-	0.12	[48]
	DA	urine plasma	V_sample:V_MeOH:V_H₂O=1:49:50 V_sample:V_MeOH=1:2	none none	Phenomenex Synergi Hydro-RP (50 mm×2.0 mm, 2.5 μm)	0.31-16 7.8 -1000	- -	[49]
	DA	blood	V_sample:V_formic_acid:V_H₂O=50:1:50	SPE (HILIC cartridge)	Agilent Zorbax SB-C8 (50 mm×2.1 mm, 1.8 μm)	1.0-10.6	0.17	[50]
CTX	MC-LR, MC-RR, MC-LA,	urine	V_sample:V_H₂O=1:24	SPE (C18 cartridge)	Waters HSS T3 C18 (50 mm×3 mm, 1.8 μm)	0.5-20	0.05, 0.05, 0.13, 0.14, 0.13, 0.05	[51]
	MC-LF, MC-LW, MC-YR	plasma, serum	V_sample:V₁₀₀_nmol/L_ZnSO₄=1:5	SPE (C18 cartridge)		0.25-10	0.08, 0.08, 0.30, 0.30, 0.30, 0.08

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生物样品中大田软海绵酸类毒素代谢规律及检测方法的研究进展

Progress on the metabolic rules and detection methods for okadaic acid related toxins in biological samples

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