植物中27种典型药品及个人护理品多残留检测方法的建立及其在芽苗菜中迁移规律的分析

doi:10.3724/SP.J.1123.2022.09017

摘要/Abstract

摘要：

建立了一种基于超高效液相色谱-串联质谱同时检测植物体内27种典型药品及个人护理品(PPCPs)残留的分析方法,经HLB萃取小柱对植物体内PPCPs富集净化,以BEH C18色谱柱(100 mm×2.1 mm, 1.7 μm)分离,以0.1%甲酸水溶液-乙腈为流动相梯度洗脱,电喷雾电离质谱正离子多反应监测(MRM)模式下分析。方法学考察表明,植物体中27种PPCPs的检出限为0.01~0.30 μg/kg;定量限为0.03~0.98 μg/kg;在各自的检测范围内有良好的线性关系(r²>0.99),平均回收率为80.8%~122.3%, 相对标准偏差 (RSD)为1.0%~9.9%。使用本方法检测生长在不同含量PPCPs培养基中的芽苗菜,结果发现在低含量PPCPs培养基中生长的芽苗菜体内检出了10种PPCPs;在中含量PPCPs培养基中生长的芽苗菜体内检出13种PPCPs;在高含量PPCPs培养基中生长的芽苗菜体内检出19种PPCPs。结果表明在有PPCPs污染的水体中生长的植物或是用含有被PPCPs污染的水源灌溉的植物会吸收并积累PPCPs,且植物对PPCPs的吸收种类及吸收量与外界PPCPs的水平有着密切关系。通过对植物根、茎、叶中PPCPs含量的分析发现,除豪莫西布曲明(叶>茎>根)、格列苯脲(根>叶>茎)外,其余吸收的PPCPs在植物组织间的含量分布均为根>茎>叶,表明PPCPs在植物体内的分布存在差异。通过计算PPCPs在植物体内的迁移因子(TF)发现,不同PPCPs在植物体内的迁移能力有着明显差异,豪莫西布曲明的TF=2.34,氯代西布曲明的TF=1.25,均>1,表明在植物体内发生迁移的药物中,豪莫西布曲明与氯代西布曲明在芽苗菜体内迁移能力最强,盐酸尼卡地平以及马来酸氯苯那敏迁移能力次之,金刚烷胺、N-单去甲基西布曲明、卡马西平以及氟甲喹等药物迁移能力最弱。PPCPs一旦被吸收后会转移到植物的茎或(和)叶中积累,并对植物其他器官造成污染而带来潜在危害;因此,在后续研究中应重点关注豪莫西布曲明、氯代西布曲明等PPCPs在植物体内的迁移。

关键词: 药品及个人护理品, 超高效液相色谱-串联质谱法, 芽苗菜, 迁移因子

Abstract:

An analytical method based on ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of 27 pharmaceutical and personal-care product (PPCP) residues in plants. The enrichment and cleanup of PPCPs in plants were achieved using an HLB extraction column, and the separation was performed on a BEH C18 column (100 mm×2.1 mm, 1.7 μm) with 0.1% formic acid water-acetonitrile as the mobile phase via gradient elution. PPCPs were detected with electrospray ionization mass spectrometry in positive-ion multiple-reaction monitoring (MRM) mode. The limits of detection and quantification of the 27 PPCPs in plants were 0.01-0.30 μg/kg and 0.03-0.98 μg/kg, respectively. Good linearities were observed with coefficients of determination (r²) >0.99. The spiked recoveries were between 80.8% and 122.3% with relative standard deviations (RSDs) between 1.0% and 9.9%. The method was subsequently used to study sprouts grown in different concentrations of PPCPs. A total of 10 PPCPs were detected in sprouts grown in medium with a low concentration PPCPs, 13 PPCPs were detected in sprouts grown in medium with a moderate concentration of PPCPs, and 19 PPCPs were detected in sprouts grown in medium with a high concentration of PPCPs. These results showed that plants grown in water bodies contaminated with PPCPs or irrigated with water contaminated with PPCPs absorbed and accumulated these substances and that the amount and type of PPCPs absorbed by plants were closely related to the levels of PPCPs in the external environment. Analysis of the contents of PPCPs in different plant tissues revealed a general distribution of root>stem>leaf. Haemosibutramine showed a tissue distribution of leaf>stem>root, while glibenclamide showed a distribution of root>leaf>stem; these results revealed differences in the distribution of PPCPs in plants. Calculation of the transfer factor (TF) of the PPCPs in plants demonstrated significant differences in the transferability of different PPCPs, with TF=2.34 for haemosibutramine and TF=1.25 for chlorosibutramine. The results showed that among the drugs that migrated in plants, haemonosibutramine and chlorosibutramine had the strongest migration ability in sprouts, followed by nicardipine and chlorpheniramine maleate, and amantadine, N-monodesmethyl sibutramine, carbamazepine and flumequine had the weakest migration ability. Once absorbed, these compounds were transferred to the stems and/or leaves, where they accumulate and cause potential harm by contaminating other plant organs. Therefore, PPCPs such as homosibutramine and chlorosibutramine, which easily migrate in plants, should be given extra attention in future studies. The method is simple in pre-treatment, sensitive and accurate, and can be widely applied to the detection of PPCP residues in plant samples.

Key words: pharmaceuticals and personal care products (PPCPs), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), sprouts, transfer factors

中图分类号:

O658

曾永福, 陈美芳, 邵雨, 闫永欢, 张海超, 王敬, 艾连峰, 康维钧. 植物中27种典型药品及个人护理品多残留检测方法的建立及其在芽苗菜中迁移规律的分析[J]. 色谱, 2023, 41(5): 386-396.

ZENG Yongfu, CHEN Meifang, SHAO Yu, YAN Yonghuan, ZHANG Haichao, WANG Jing, AI Lianfeng, KANG Weijun. Development of a multi-residue detection method for 27 typical pharmaceuticals and personal-care products in plants and analysis of their migration patterns in sprouts[J]. Chinese Journal of Chromatography, 2023, 41(5): 386-396.

图/表 11

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Drug	CAS number	Drug type	Ionization mode	Parent ion (m/z)	Daughter ion (m/z)	Collision energy/eV	t_R/ min
Nisoldipine (尼索地平)	63675-72-9	antihypertensive drug	[M+H]⁺	389.2	239.2^*/195.2	21/42	6.17
Nimodipine (尼莫地平)	66085-59-4	antihypertensive drug	[M+H]⁺	419.2	343.2^*/301.1	14/26	3.12
Nitrendipine (尼群地平)	39562-70-4	antihypertensive drug	[M+H]⁺	361.2	315.1^*/329.2	14/15	5.85
Nicardipine hydrochloride	54527-84-3	antihypertensive drug	[M+H]⁺	480.3	315.2^*/359.2	25/25	4.51
(盐酸尼卡地平)
Minoxidil (米诺地尔)	38304-91-5	antihypertensive drug	[M+H]⁺	210.2	164.2^*/110.1	22/25	3.14
Indapamide (吲达帕胺)	26807-65-8	antihypertensive drug	[M+H]⁺	366.1	132.1^*/91.1	14/44	4.72
Lovastatin (洛伐他汀)	75330-75-5	lipid-lowering drug	[M+H]⁺	459.3	357.3^*/342.2	24/26	5.67
Mevastatin (美伐他汀)	73573-88-3	lipid-lowering drug	[M+H]⁺	391.3	185.2^*/159.1	12/28	6.48
Atorvastatin calcium (阿托伐他汀钙)	134523-03-8	lipid-lowering drug	[M+H]⁺	559.3	440.3^*/292.3	23/33	5.71
Sibutramine (西布曲明)	106650-56-0	weight-reducing aid	[M+H]⁺	280.2	125.1^*/139.1	25/15	4.75
Chlorosibutramine (氯代西布曲明)	84485-08-5	weight-reducing aid	[M+H]⁺	314.2	159.0^*/173.0	27/17	4.92
N-Monodesmethyl sibutramine	84467-94-7	weight-reducing aid	[M+H]⁺	266.2	125.1^*/139.1	24/14	4.65
(N-单去甲基西布曲明)
N,N-Bis-desmethyl sibutramine	84484-78-6	weight-reducing aid	[M+H]⁺	252.2	125.0^*/139.1	22/12	4.58
(N,N-双去甲基西布曲明)
Haemosibutramine (豪莫西布曲明)	935888-80-5	weight-reducing aid	[M+H]⁺	294.3	125.1^*/139.1	26/17	4.85
Glibenclamide (格列苯脲)	10238-21-8	hypolycemic agent	[M+H]⁺	494.2	369.1^*/169.1	15/36	5.78
Glimepiride (格列美脲)	93479-97-1	hypolycemic agent	[M+H]⁺	491.3	352.2^*/126.1	15/27	5.94
Repaglinide (瑞格列奈)	135062-02-1	hypolycemic agent	[M+H]⁺	453.3	230.2^*/162.2	28/21	4.95
Gliclazide (格列齐特)	21187-98-4	hypolycemic agent	[M+H]⁺	324.2	127.2^*/110.1	18/22	5.43
Diphenhydramine (苯海拉明)	58-73-1	antihistamine drug	[M+H]⁺	256.2	167.2^*/152.1	14/37	4.19
Chlorpheniramine maleate	113-92-8	antihistamine drug	[M+H]⁺	275.2	230.1^*/167.1	17/38	3.61
(马来酸氯苯那敏)
Flumequine (氟甲喹)	42835-25-6	antibacterial drug	[M+H]⁺	262.1	244.1^*/220.0	21/8	4.72
Sparfloxacin (司帕沙星)	110871-86-8	antibacterial drug	[M+H]⁺	393.2	292.1^*/149.0	26/55	3.45
Amantadine (金刚烷胺)	768-94-5	antiviral drug	[M+H]⁺	180.2	163.2^*/81.1	17/23	3.73
Carbamazepine (卡马西平)	298-46-4	antiepileptic drug	[M+H]⁺	237.2	194.2^*/179.2	19/34	4.56
Cortisone (可的松)	53-06-5	adrenocortical hormone	[M+H]⁺	361.2	163.1^*/121.1	23/29	4.24
Testosterone propionate (丙酸睾酮)	57-85-2	androgens	[M+H]⁺	345.2	97.1^*/109.1	24/31	7.24
Danazol (达那唑)	17230-88-5	antiestrogenic drug	[M+H]⁺	338.3	120.1^*/148.2	30/25	6.29

Drug	CAS number	Drug type	Ionization mode	Parent ion (m/z)	Daughter ion (m/z)	Collision energy/eV	t_R/ min
Nisoldipine (尼索地平)	63675-72-9	antihypertensive drug	[M+H]⁺	389.2	239.2^*/195.2	21/42	6.17
Nimodipine (尼莫地平)	66085-59-4	antihypertensive drug	[M+H]⁺	419.2	343.2^*/301.1	14/26	3.12
Nitrendipine (尼群地平)	39562-70-4	antihypertensive drug	[M+H]⁺	361.2	315.1^*/329.2	14/15	5.85
Nicardipine hydrochloride	54527-84-3	antihypertensive drug	[M+H]⁺	480.3	315.2^*/359.2	25/25	4.51
(盐酸尼卡地平)
Minoxidil (米诺地尔)	38304-91-5	antihypertensive drug	[M+H]⁺	210.2	164.2^*/110.1	22/25	3.14
Indapamide (吲达帕胺)	26807-65-8	antihypertensive drug	[M+H]⁺	366.1	132.1^*/91.1	14/44	4.72
Lovastatin (洛伐他汀)	75330-75-5	lipid-lowering drug	[M+H]⁺	459.3	357.3^*/342.2	24/26	5.67
Mevastatin (美伐他汀)	73573-88-3	lipid-lowering drug	[M+H]⁺	391.3	185.2^*/159.1	12/28	6.48
Atorvastatin calcium (阿托伐他汀钙)	134523-03-8	lipid-lowering drug	[M+H]⁺	559.3	440.3^*/292.3	23/33	5.71
Sibutramine (西布曲明)	106650-56-0	weight-reducing aid	[M+H]⁺	280.2	125.1^*/139.1	25/15	4.75
Chlorosibutramine (氯代西布曲明)	84485-08-5	weight-reducing aid	[M+H]⁺	314.2	159.0^*/173.0	27/17	4.92
N-Monodesmethyl sibutramine	84467-94-7	weight-reducing aid	[M+H]⁺	266.2	125.1^*/139.1	24/14	4.65
(N-单去甲基西布曲明)
N,N-Bis-desmethyl sibutramine	84484-78-6	weight-reducing aid	[M+H]⁺	252.2	125.0^*/139.1	22/12	4.58
(N,N-双去甲基西布曲明)
Haemosibutramine (豪莫西布曲明)	935888-80-5	weight-reducing aid	[M+H]⁺	294.3	125.1^*/139.1	26/17	4.85
Glibenclamide (格列苯脲)	10238-21-8	hypolycemic agent	[M+H]⁺	494.2	369.1^*/169.1	15/36	5.78
Glimepiride (格列美脲)	93479-97-1	hypolycemic agent	[M+H]⁺	491.3	352.2^*/126.1	15/27	5.94
Repaglinide (瑞格列奈)	135062-02-1	hypolycemic agent	[M+H]⁺	453.3	230.2^*/162.2	28/21	4.95
Gliclazide (格列齐特)	21187-98-4	hypolycemic agent	[M+H]⁺	324.2	127.2^*/110.1	18/22	5.43
Diphenhydramine (苯海拉明)	58-73-1	antihistamine drug	[M+H]⁺	256.2	167.2^*/152.1	14/37	4.19
Chlorpheniramine maleate	113-92-8	antihistamine drug	[M+H]⁺	275.2	230.1^*/167.1	17/38	3.61
(马来酸氯苯那敏)
Flumequine (氟甲喹)	42835-25-6	antibacterial drug	[M+H]⁺	262.1	244.1^*/220.0	21/8	4.72
Sparfloxacin (司帕沙星)	110871-86-8	antibacterial drug	[M+H]⁺	393.2	292.1^*/149.0	26/55	3.45
Amantadine (金刚烷胺)	768-94-5	antiviral drug	[M+H]⁺	180.2	163.2^*/81.1	17/23	3.73
Carbamazepine (卡马西平)	298-46-4	antiepileptic drug	[M+H]⁺	237.2	194.2^*/179.2	19/34	4.56
Cortisone (可的松)	53-06-5	adrenocortical hormone	[M+H]⁺	361.2	163.1^*/121.1	23/29	4.24
Testosterone propionate (丙酸睾酮)	57-85-2	androgens	[M+H]⁺	345.2	97.1^*/109.1	24/31	7.24
Danazol (达那唑)	17230-88-5	antiestrogenic drug	[M+H]⁺	338.3	120.1^*/148.2	30/25	6.29

Drug	Spiked levels/ (μg/L)	MEs/%	RSDs/%	Drug	Spiked levels/ (μg/L)	MEs/%	RSDs/%
Nisoldipine	5/50/150	116.1/109.3/96.4	6.1/7.8/5.5	N-Monodesmethyl	5/50/150	115.1/119.0/94.5	5.4/5.2/5.9
Nimodipine	5/50/150	97.3/85.7/81.2	6.9/5.3/4.8	sibutramine
Nitrendipine	5/50/150	116.1/101.2/96.1	4.6/7.7/4.4	N,N-Bis-desmethyl	5/50/150	106.2/98.1/95.7	5.3/2.8/7.2
Nicardipine	5/50/150	156.8/149.0/137.9	5.1/7.4/2.1	sibutramine
hydrochloride				Haemosibutramine	5/50/150	119.4/112.8/94.7	5.6/2.9/2.6
Minoxidil	5/50/150	91.3/85.4/87.1	4.2/2.7/3.4	Atorvastatin calcium	5/50/150	64.8/69.3/67.8	4.4/6.3/8.3
Indapamide	5/50/150	106.7/92.7/94.1	4.8/6.5/2.6	Glibenclamide	5/50/150	86.5/96.3/97.7	3.7/5.7/4.6
Lovastatin	5/50/150	119.2/118.2/114.9	6.1/5.8/3.3	Glimepiride	5/50/150	93.2/108.7/102.8	2.9/6.1/8.7
Mevastatin	5/50/150	90.2/88.9/84.7	3.8/3.7/2.5	Repaglinide	5/50/150	104.7/104.6/98.0	4.5/3.5/4.8
Amantadine	5/50/150	130.0/147.3/136.5	3.7/4.2/8.1	Gliclazide	5/50/150	103.9/97.3/94.2	4.5/3.4/2.7
Diphenhydramine	5/50/150	138.5/130.5/127.5	6.1/3.9/5.7	Cortisone	5/50/150	124.8/123.9/127.6	6.9/5.1/2.2
Chlorpheniramine	5/50/150	107.0/104.3/96.5	4.9/5.1/6.2	Danazol	5/50/150	95.1/98.4/82.1	6.6/4.3/2.8
maleate				Testosterone	5/50/150	102.3/96.6/90.8	7.4/5.4/8.8
Carbamazepine	5/50/150	95.1/97.2/82.5	2.7/6.2/3.3	propionate
Sibutramine	5/50/150	90.3/92.7/94.7	3.1/4.1/5.6	Flumequine	5/50/150	105.6/106.9/104.0	3.0/2.1/2.7
Chlorosibutramine	5/50/150	100.7/86.8/87.5	7.9/8.1/6.9	Sparfloxacin	5/50/150	68.2/66.7/63.5	8.2/7.1/4.4

Drug	Spiked levels/ (μg/L)	MEs/%	RSDs/%	Drug	Spiked levels/ (μg/L)	MEs/%	RSDs/%
Nisoldipine	5/50/150	116.1/109.3/96.4	6.1/7.8/5.5	N-Monodesmethyl	5/50/150	115.1/119.0/94.5	5.4/5.2/5.9
Nimodipine	5/50/150	97.3/85.7/81.2	6.9/5.3/4.8	sibutramine
Nitrendipine	5/50/150	116.1/101.2/96.1	4.6/7.7/4.4	N,N-Bis-desmethyl	5/50/150	106.2/98.1/95.7	5.3/2.8/7.2
Nicardipine	5/50/150	156.8/149.0/137.9	5.1/7.4/2.1	sibutramine
hydrochloride				Haemosibutramine	5/50/150	119.4/112.8/94.7	5.6/2.9/2.6
Minoxidil	5/50/150	91.3/85.4/87.1	4.2/2.7/3.4	Atorvastatin calcium	5/50/150	64.8/69.3/67.8	4.4/6.3/8.3
Indapamide	5/50/150	106.7/92.7/94.1	4.8/6.5/2.6	Glibenclamide	5/50/150	86.5/96.3/97.7	3.7/5.7/4.6
Lovastatin	5/50/150	119.2/118.2/114.9	6.1/5.8/3.3	Glimepiride	5/50/150	93.2/108.7/102.8	2.9/6.1/8.7
Mevastatin	5/50/150	90.2/88.9/84.7	3.8/3.7/2.5	Repaglinide	5/50/150	104.7/104.6/98.0	4.5/3.5/4.8
Amantadine	5/50/150	130.0/147.3/136.5	3.7/4.2/8.1	Gliclazide	5/50/150	103.9/97.3/94.2	4.5/3.4/2.7
Diphenhydramine	5/50/150	138.5/130.5/127.5	6.1/3.9/5.7	Cortisone	5/50/150	124.8/123.9/127.6	6.9/5.1/2.2
Chlorpheniramine	5/50/150	107.0/104.3/96.5	4.9/5.1/6.2	Danazol	5/50/150	95.1/98.4/82.1	6.6/4.3/2.8
maleate				Testosterone	5/50/150	102.3/96.6/90.8	7.4/5.4/8.8
Carbamazepine	5/50/150	95.1/97.2/82.5	2.7/6.2/3.3	propionate
Sibutramine	5/50/150	90.3/92.7/94.7	3.1/4.1/5.6	Flumequine	5/50/150	105.6/106.9/104.0	3.0/2.1/2.7
Chlorosibutramine	5/50/150	100.7/86.8/87.5	7.9/8.1/6.9	Sparfloxacin	5/50/150	68.2/66.7/63.5	8.2/7.1/4.4

Drug	Linear equation	Linear range/(μg/L)	r²	LOD/(μg/kg)	LOQ/(μg/kg)
Nisoldipine	y=1.1×10⁵x-1.5×10⁴	0.5-200	0.9997	0.18	0.55
Minoxidil	y=4.7×10⁵x+2.2×10⁵	0.1-150	0.9997	0.10	0.28
Nimodipine	y=3.7×10⁴x+4.8×10⁴	1.0-200	0.9999	0.24	0.72
Nicardipine hydrochloride	y=1.1×10⁵x+1.9×10⁵	0.1-200	0.9940	0.18	0.55
Indapamide	y=7.2×10⁴x-1.6×10⁴	0.5-200	0.9978	0.20	0.62
Lovastatin	y=1.4×10⁴x+3.3×10³	1.0-100	0.9970	0.28	0.84
Mevastatin	y=2.7×10⁴x-1.4×10⁴	0.5-100	0.9980	0.25	0.74
Amantadine	y=1.2×10⁵x+4.2×10⁵	0.1-200	0.9983	0.18	0.55
Diphenhydramine	y=2.1×10⁵x-1.2×10⁵	1.0-300	0.9960	0.15	0.46
Chlorpheniramine maleate	y=5.2×10⁵x+4.7×10⁵	0.1-200	0.9971	0.09	0.28
Carbamazepine	y=5.6×10⁶x+7.5×10⁵	0.1-100	0.9963	0.01	0.03
Sibutramine	y=2.9×10⁴x+1.7×10³	1.0-200	0.9980	0.25	0.74
Haemosibutramine	y=7.8×10⁵x+4.6×10⁵	0.5-150	0.9984	0.06	0.18
Chlorosibutramine	y=1.7×10⁵x-5.0×10⁵	1.0-100	0.9962	0.18	0.56
N-Monodesmethyl sibutramine	y=8.8×10³x+7.4×10³	0.5-100	0.9981	0.30	0.98
N,N-Bis-desmethyl sibutramine	y=4.2×10⁵x+1.1×10⁵	0.5-100	0.9997	0.10	0.30
Glibenclamide	y=6.8×10⁴x+3.6×10³	1.0-150	0.9963	0.20	0.62
Glimepiride	y=3.0×10⁴x+2.0×10³	1.0-150	0.9912	0.25	0.73
Gliclazide	y=2.9×10⁵x+4.5×10³	1.0-100	0.9999	0.15	0.46
Repaglinide	y=5.3×10⁵x+8.7×10³	0.1-100	0.9973	0.09	0.27
Danazol	y=6.8×10⁵x+1.4×10⁴	0.1-100	0.9964	0.08	0.25
Testosterone propionate	y=2.8×10⁴x-4.3×10³	0.5-100	0.9983	0.25	0.74
Cortisone	y=2.4×10⁵x+1.1×10⁴	0.5-100	0.9961	0.15	0.46
Flumequine	y=2.4×10⁴x-5.6×10²	1.0-100	0.9983	0.27	0.81
Sparfloxacin	y=7.9×10⁴x-4.0×10⁴	0.5-200	0.9982	0.20	0.62
Atorvastatin calcium	y=2.2×10⁵x-4.6×10⁵	1.0-200	0.9970	0.15	0.46
Nitrendipine	y=1.4×10⁴x+1.1×10⁴	1.0-200	0.9998	0.28	0.84