基于UPLC-Q-TOF-MS与HPLC-QQQ-MS/MS对化妆品中23种局部麻醉药进行筛查与测定

doi:10.3969/j.issn.2097-2806.2026.02.015

摘要/Abstract

摘要：

实验室建立了一种高效的反相超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF-MS）定性方法，用于筛查化妆品中超过2 000种风险物质（包括局部麻醉药，LAs），该方法已成功应用于实际样品分析。该研究旨在开发一种更简便的高效液相色谱-三重四极杆串联质谱（HPLC-QQQ-MS/MS）方法，用于LAs的定量测定。样品经甲醇超声提取后，采用安捷伦Poroshell 120 EC-C₁₈色谱柱（2.1 mm × 100 mm，2.7 μm）进行分离，以0.1%甲酸水溶液和甲醇为流动相进行梯度洗脱，采用外标法进行定量分析。结果表明，23种LAs在12 min内实现有效分离，在对应浓度范围内线性关系良好，相关系数均大于0.99；检出限为0.002 5~0.05 μg/g，定量限为0.01~0.1 μg/g；在5种空白化妆品基质中，23种LAs的平均回收率为80.68%~117.57%，相对标准偏差均小于5.98%。该方法精密度良好、准确度高，适用于5种化妆品基质中LAs的测定。

关键词: 局部麻醉药, 分析化学, 超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF-MS）, 高效液相色谱-三重四极杆串联质谱（HPLC-QQQ-MS/MS）

Abstract:

The laboratory established an efficient reversed-phase ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS）qualitative method for screening more than 2 000 kinds of risk substances（including local anesthetics, LAs）in cosmetics, which has been successfully applied in the analysis of actual samples. This work aims to develop a more convenient high performance liquid chromatography triple quadrupole mass spectrometry（HPLC-QQQ-MS/MS）method for the quantitative determination of LAs. Samples were ultrasonically extracted with methanol, separated on an Agilent Poroshell 120 EC-C₁₈ column（2.1 mm × 100 mm, 2.7 μm）, and eluted with a gradient mobile phase consisting of 0.1% formic acid aqueous solution and methanol. Quantification was performed using the external standard method. The results show that all 23 LAs are effectively separated within 12 minutes, with good linearity in the corresponding concentration ranges and the correlation coefficients all greater than 0.99. The limits of detection（LOD）range from 0.002 5 to 0.05 μg/g, and the limits of quantification（LOQ）range from 0.01 to 0.1 μg/g. The average recoveries of the 23 LAs in 5 blank cosmetic matrices are 80.68%-117.57%, with the relative standard deviations（RSDs）less than 5.98%. This method has good precision and high accuracy, and is suitable for the determination of LAs in 5 cosmetic matrices.

Key words: local anesthetics, chemical analysis, ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS）, high performance liquid chromatography triple quadrupole mass spectrometry（HPLC-QQQ-MS/MS）

中图分类号:

TQ658

杨若彤, 吴方园, 徐廣谦, 郭桂文, 王海燕, 贾凌云. 基于UPLC-Q-TOF-MS与HPLC-QQQ-MS/MS对化妆品中23种局部麻醉药进行筛查与测定[J]. 日用化学工业（中英文）, 2026, 56(2): 260-270.

Ruotong Yang, Fangyuan Wu, Guangqian Xu, Guiwen Guo, Haiyan Wang, Lingyun Jia. Screening and determination of 23 local anesthetics in cosmetics using UPLC-Q-TOF-MS and HPLC-QQQ-MS/MS[J]. China Surfactant Detergent & Cosmetics, 2026, 56(2): 260-270.

图/表 9

No.	Lotion		Cream		Gel		Oil		Powder		LOD/ （μg/g）	LOQ/ （μg/g）
No.	Linear equation	r	Linear equation	r	Linear equation	r	Linear equation	r	Linear equation	r	LOD/ （μg/g）	LOQ/ （μg/g）
1	y=2 769x+313	0.995 9	y=20 514x+222	0.998 1	y=20 332x+353	0.9971	y=11 906x-24 142	0.997 0	y=16 005x+834	0.993 8	0.01	0.025
2	y=3 596x-651	0.992 2	y=21 525x+1 357	0.996 3	y=21 504x+306	0.9992	y=24 247x+9 634	0.997 9	y=15 804x+1 225	0.993 9	0.006	0.02
3	y=7 203x+107	0.999 6	y=7 911x-546	0.999 5	y=8 309x-3 537	0.9999	y=17 451x-10 680	0.997 3	y=14 822x-5 011	0.998 1	0.025	0.1
4	y=132 147x-998	0.999 2	y=122 344x+2 480	0.995 3	y=140 572x+2 552	0.9985	y=278 206x+39 388	0.993 0	y=126 860x+2 475	0.995 9	0.002 5	0.005
5	y=181 138x-83	0.998 8	y=182 089x+649	0.999 2	y=182 374x+2 203	0.9971	y=232 382x+151 973	0.993 4	y=121 044x+2 878	0.994 0	0.002 5	0.005
6	y=1 098x-21	0.994 9	y=1 090x-321	0.998 9	y=1 023x+1 931	0.9980	y=6 132x+4 465	0.997 5	y=1 005x+1 089	0.991 4	0.05	0.1
7	y=19 024x+687	0.994 8	y=18 581x-1 419	0.996 6	y=20 058x-16	0.9950	y=18 801x+17 176	0.997 8	y=4 889x+5 615	0.993 7	0.005	0.025
8	y=17 328x+144	0.997 0	y=14 511x-187	0.998 9	y=17 547x+721	0.9992	y=20 757x-16 492	0.993 2	y=19 127x+731	0.992 0	0.005	0.025
9	y=162 451x+3 558	0.997 5	y=120 894x+795	0.999 4	y=161 256x+8 905	0.9957	y=176 537x+158 195	0.992 9	y=77 893x+16 549	0.990 1	0.005	0.025
10	y=88 897x+17 572	0.997 9	y=61 738x+7 070	0.994 3	y=89 474x+36 148	0.9949	y=102 930x+56 070	0.993 7	y=69 698x+10 303	0.992 8	0.005	0.025
11	y=39 477x+506	0.998 6	y=40 530x+592	0.995 9	y=36 668x+1 225	0.9973	y=1 435x-1 937	0.993 9	y=44 163x-1 183	0.997 6	0.01	0.03
12	y=6 401x-397	0.997 6	y=7 217x+94	0.999 0	y=6 907x-460	0.9972	y=63 891x+464	0.991 4	y=7 082x+441	0.997 4	0.02	0.05
13	y=716x+229	0.997 3	y=725x+2 255	0.995 7	y=651x+536	0.9926	y=1 040x+419	0.993 6	y=158 812x+3 719	0.990 6	0.025	0.05
14	y=72 613x+3 039	0.994 2	y=64 075x+796	0.998 5	y=61 454x+1 438	0.9933	y=86 627x+71 404	0.998 6	y=157 162x+4 057	0.990 4	0.002 5	0.01
15	y=36 323x+3 125	0.999 2	y=33 109x-3 211	0.999 1	y=36 910x+4 529	0.9990	y=45 302x+27 275	0.997 5	y=27 520x+609	0.994 3	0.005	0.025
16	y=29 030x+3 013	0.997 1	y=20 748x+6 754	0.995 9	y=21 832x+5 406	0.9916	y=41 723x+13 281	0.990 8	y=24 930x+1 377	0.991 3	0.005	0.02
17	y=271 458x+5 093	0.994 7	y=227 299x+21 757	0.999 2	y=246 299x+11 845	0.9930	y=192 135x+14 084	0.992 1	y=150 443x+12 488	0.990 0	0.005	0.025
18	y=30 188x+67	0.999 4	y=31 528x+5 638	0.997 9	y=31 870x+3 460	0.9994	y=31 920x+12 809	0.998 9	y=24 352x+647	0.998 9	0.01	0.03
19	y=40 949x+5 432	0.991 1	y=47 461x+4 512	0.998 0	y=43 106x+5 827	0.9956	y=20 473x+2 847	0.995 0	y=30 531x+1 459	0.994 2	0.005	0.025
20	y=26 281x+2 147	0.991 8	y=26 394x+443	0.997 1	y=19 371x+1 249	0.9944	y=30 791x+3 835	0.992 3	y=37 154x+764	0.993 9	0.004 5	0.015
21	y=17 880x+423	0.999 9	y=19 342x+3 624	0.999 2	y=18 840x+3 204	0.9994	y=174 414x-11 574	0.999 1	y=9 637x+3 698	0.999 7	0.01	0.025
22	y=84 334x+19 710	0.999 5	y=149 989x+2 055	0.998 8	y=147 658x+5 085	0.9971	y=128 251x+1 701	0.992 1	y=106 380x+3 856	0.991 9	0.01	0.05
23	y=40 330x-8 018	0.998 1	y=95 197x+1 258	0.998 6	y=95 204x+1 323	0.9984	y=116 870x+90 393	0.997 3	y=41 016x+1 440	0.992 2	0.01	0.05

No.	Concentration	Lotion		Cream		Gel		Oil		Power
No.	Concentration	Recovery/%	RSD/%	Recovery/%	RSD/%	Recovery/%	RSD/%	Recovery/%	RSD/%	Recovery/%	RSD/%
1	Low	89.69	2.61	89.63	4.13	84.31	1.61	107.27	3.16	110.36	1.34
1	High	83.34	2.48	94.93	1.41	84.97	2.05	107.27	1.10	92.96	0.83
2	Low	89.88	3.57	95.57	2.51	85.11	1.73	108.06	3.42	100.14	1.96
2	High	98.17	0.79	99.97	1.13	91.81	1.74	97.61	1.29	84.93	1.15
3	Low	87.67	1.13	89.66	1.68	95.95	1.42	105.68	0.99	81.41	1.77
3	High	90.04	2.65	96.06	1.47	98.97	2.38	108.32	4.24	90.20	1.82
4	Low	99.04	2.06	113.01	3.63	88.91	3.41	95.79	2.88	90.73	0.70
4	High	89.56	2.36	89.80	0.92	88.58	4.06	100.20	2.85	83.89	0.68
5	Low	92.98	1.08	93.76	0.43	86.42	2.05	99.47	2.34	83.99	0.78
5	High	90.45	2.23	90.23	1.78	101.07	2.33	92.27	2.44	103.67	1.90
6	Low	95.36	3.49	94.83	3.00	96.48	0.83	100.37	3.00	90.06	1.87
6	High	98.23	2.01	92.96	1.26	91.31	2.13	102.27	1.35	90.98	1.01
7	Low	87.54	2.42	99.73	2.24	90.17	4.03	97.18	4.00	105.24	1.33
7	High	89.76	2.44	107.01	2.17	89.65	1.60	104.41	1.76	91.05	1.70
8	Low	87.18	3.80	106.05	1.80	87.75	2.48	105.31	2.36	90.53	2.13
8	High	87.58	3.95	102.04	1.63	87.45	1.67	110.68	1.10	95.39	2.00
9	Low	100.25	2.35	115.39	2.72	89.37	2.92	106.65	3.51	95.76	1.16
9	High	89.77	2.25	102.01	1.13	86.54	1.69	112.99	2.12	109.97	1.74
10	Low	97.05	3.62	113.85	0.38	82.46	1.87	107.17	3.24	102.87	1.80
10	High	97.04	1.52	99.46	1.02	86.16	1.10	112.53	0.96	86.11	0.21
11	Low	92.68	3.21	105.56	3.49	86.13	4.07	113.18	0.36	87.93	2.97
11	High	91.30	1.32	87.88	3.90	90.53	2.96	107.94	3.27	98.06	2.78
12	Low	94.17	3.87	100.62	1.88	90.76	1.21	109.58	4.62	86.51	4.44
12	High	89.34	1.64	86.07	3.83	86.74	2.25	104.61	2.56	82.69	4.12
13	Low	97.44	3.37	92.62	2.84	100.36	1.53	112.47	2.98	116.10	2.70
13	High	95.69	3.66	85.28	2.88	97.25	2.06	112.70	2.66	98.83	1.30
14	Low	101.81	2.06	105.25	1.96	89.59	2.91	104.55	1.74	95.74	3.26
14	High	82.74	1.47	89.27	0.73	102.89	1.32	111.90	1.53	93.72	1.90
15	Low	91.13	3.87	103.37	1.64	96.67	1.48	113.13	2.42	82.07	4.73
15	High	88.66	1.32	100.31	2.26	95.97	1.31	108.60	2.45	80.45	0.63
16	Low	101.23	1.18	114.26	3.60	94.68	3.81	105.51	3.38	88.59	0.86
16	High	88.10	2.71	91.35	0.71	93.82	1.14	108.89	1.24	105.40	1.12
17	Low	94.19	0.92	97.03	1.89	91.73	1.49	107.76	1.43	109.32	4.94
17	High	93.12	1.32	85.71	1.93	98.77	1.76	101.60	2.12	100.58	0.85
18	Low	90.34	0.97	91.85	4.25	91.61	3.53	100.45	2.12	91.53	3.03
18	High	91.65	1.20	95.91	2.18	87.49	2.73	99.42	1.68	89.32	2.41
19	Low	101.53	1.23	112.23	4.71	102.31	2.58	110.64	2.26	107.54	3.37
19	High	89.92	2.72	99.86	2.52	99.40	3.01	110.21	2.54	95.07	2.53
20	Low	97.20	3.34	100.56	3.63	92.99	3.17	103.58	3.25	90.70	4.15
20	High	90.16	2.67	88.33	3.40	109.56	2.77	109.66	3.41	112.15	2.57
21	Low	91.87	2.38	88.93	1.85	101.55	2.55	109.44	4.23	96.40	3.94
21	High	89.23	2.42	89.15	3.36	92.75	1.96	106.20	1.72	95.70	3.05
22	Low	103.85	1.19	91.91	2.68	90.41	1.84	108.34	1.85	84.16	4.21
22	High	107.39	2.47	84.65	3.47	90.93	2.08	109.27	2.50	83.45	2.28
23	Low	99.33	1.98	97.41	2.87	88.78	2.52	92.26	3.93	109.25	3.89
23	High	88.70	1.36	94.85	1.63	105.04	1.19	98.40	1.68	101.86	1.82

No.	Concentration	Lotion		Cream		Gel		Oil		Powder
No.	Concentration	Recovery/%	RSD/%	Recovery/%	RSD/%	Recovery/%	RSD/%	Recovery/%	RSD/%	Recovery/%	RSD/%
1	Low	90.25	3.94	90.74	4.40	84.22	1.80	106.42	4.79	110.16	4.99
	Middle	85.71	4.73	93.25	3.36	84.20	1.76	106.31	3.79	92.54	4.98
	High	84.32	3.08	95.58	2.88	84.90	3.43	109.92	4.81	99.77	4.85
2	Low	89.07	3.48	94.39	4.54	91.76	4.89	97.85	1.70	84.74	3.23
	Middle	92.52	2.92	106.14	4.25	95.85	2.85	104.20	5.98	81.52	2.23
	High	97.90	2.01	100.55	2.67	99.38	2.84	108.47	3.39	89.93	3.03
3	Low	87.41	0.85	90.28	3.12	89.12	3.26	95.65	4.33	91.25	3.73
	Middle	86.71	2.85	90.61	2.49	88.09	1.23	100.82	3.22	83.70	2.28
	High	89.85	1.73	96.26	2.30	86.47	1.87	101.13	3.37	83.91	1.57
4	Low	98.81	2.48	112.06	3.67	100.93	3.87	93.33	2.68	104.21	2.12
	Middle	92.61	2.20	96.63	1.96	96.01	1.54	100.02	2.25	90.65	1.16
	High	90.44	2.18	90.74	1.01	92.26	0.98	101.58	3.30	91.11	0.87
5	Low	93.60	1.78	93.20	2.66	90.16	1.64	97.93	4.46	105.43	1.97
	Middle	86.54	2.70	92.97	1.87	90.24	2.83	106.03	4.57	91.24	0.87
	High	89.18	2.90	89.21	1.72	88.81	2.83	105.85	4.37	91.13	2.43
6	Low	94.89	2.69	95.29	2.95	87.78	2.76	110.48	4.05	95.54	3.75
	Middle	96.06	2.88	92.09	1.62	88.74	2.60	107.51	3.57	96.39	3.34
	High	97.22	2.81	93.89	2.01	86.39	1.91	113.64	3.86	110.48	4.05
7	Low	88.50	3.97	98.65	3.09	83.05	1.95	107.32	4.57	102.36	4.57
	Middle	84.33	4.69	101.14	1.77	85.83	2.51	113.54	2.80	86.31	3.80
	High	89.18	3.82	107.49	3.20	85.41	2.69	112.41	1.54	88.04	2.76
8	Low	88.80	2.39	104.83	3.12	91.10	4.06	109.32	4.15	97.83	1.40
	Middle	87.31	1.98	103.16	1.82	90.23	1.41	109.79	2.23	84.91	1.57
	High	88.64	2.29	101.93	2.64	86.91	1.87	106.17	3.60	82.03	2.18
9	Low	99.68	2.59	113.01	4.93	100.61	1.77	113.64	3.32	117.52	1.63
	Middle	87.86	1.87	111.04	1.04	96.33	2.35	113.13	1.21	99.63	1.83
	High	88.63	2.28	102.01	2.01	89.86	2.35	103.51	1.81	94.94	1.33
10	Low	98.91	3.15	114.39	0.88	103.31	3.09	109.85	3.61	94.49	2.41
	Middle	100.25	3.80	104.95	1.14	97.94	1.11	111.99	1.84	83.12	1.81
	High	96.67	1.77	99.46	1.96	95.72	1.60	108.20	2.72	80.68	0.69
11	Low	92.18	3.58	104.03	4.41	95.32	4.35	104.61	4.89	88.33	4.85
	Middle	88.99	3.47	93.77	4.72	94.10	4.25	108.52	3.22	105.15	2.66
	High	92.20	4.66	87.88	3.76	92.28	4.22	107.91	2.65	107.73	2.60
12	Low	95.46	2.83	100.87	3.41	99.79	2.67	103.19	3.96	100.75	4.19
	Middle	93.05	1.98	89.90	3.48	92.17	1.95	101.67	3.67	90.80	2.18
	High	90.56	3.38	85.04	3.95	88.20	2.08	99.18	3.50	89.57	2.68
13	Low	96.94	2.00	93.05	4.80	103.25	3.63	108.08	2.89	109.95	1.32
	Middle	92.71	4.22	90.96	4.73	97.43	4.76	109.73	4.04	96.05	1.72
	High	95.17	1.90	85.28	2.62	91.57	4.95	104.44	3.16	91.98	1.09
14	Low	100.74	3.58	103.97	4.56	110.32	2.04	109.42	1.50	112.92	2.42
	Middle	92.67	2.87	93.52	2.51	101.27	2.74	110.28	3.23	96.18	1.90
	High	82.57	1.23	90.07	1.35	92.80	1.69	107.33	1.54	94.71	1.29
15	Low	92.15	3.26	104.17	3.88	91.11	1.55	108.57	2.16	84.47	1.08
	Middle	89.40	3.89	101.64	4.78	90.93	2.02	107.67	1.79	82.69	1.06
	High	88.16	2.26	101.25	1.55	87.99	2.51	93.00	2.90	108.57	2.16
16	Low	99.99	2.74	112.79	3.57	105.87	4.02	98.25	4.21	102.64	2.39
	Middle	93.81	2.51	97.58	2.18	93.62	2.08	100.14	2.41	91.08	2.86
	High	89.31	1.65	91.50	1.49	85.43	1.97	97.64	2.31	87.04	1.59
17	Low	93.80	1.68	95.92	1.99	94.03	2.80	100.13	3.26	111.12	0.95
	Middle	92.29	3.26	89.83	2.22	89.67	3.11	102.55	1.90	93.11	1.95
	High	92.73	1.41	87.04	3.39	88.22	2.40	100.97	1.79	93.51	1.56
18	Low	90.70	3.08	90.14	1.90	86.73	3.20	100.13	2.93	103.30	3.39
	Middle	87.87	1.40	91.43	1.19	85.75	1.80	110.50	3.57	95.27	2.41
	High	92.36	2.01	95.91	1.76	83.42	2.26	117.57	1.28	87.93	2.35
19	Low	100.67	2.62	112.23	2.66	92.53	3.11	114.88	2.31	97.06	3.84
	Middle	93.76	2.19	105.37	3.20	88.99	2.38	115.60	2.54	87.38	3.42
	High	89.08	2.43	99.86	1.67	85.08	2.68	109.35	2.51	95.21	2.44
20	Low	95.62	1.57	105.27	1.60	99.94	2.09	98.15	5.43	92.24	0.97
	Middle	92.32	2.19	91.26	2.00	93.80	2.38	98.16	4.12	82.61	1.96
	High	89.28	1.46	88.02	2.54	88.55	2.31	95.52	4.30	86.96	2.69
21	Low	91.62	2.10	88.29	1.51	91.34	2.63	95.42	4.10	100.12	4.21
	Middle	88.49	1.32	86.67	2.05	91.15	1.31	102.08	2.93	89.14	3.50
	High	89.71	1.98	87.85	1.24	90.23	1.71	102.49	4.78	84.93	3.07
22	Low	104.74	1.09	92.23	1.27	87.08	4.12	95.13	1.64	105.80	1.73
	Middle	105.18	1.64	86.00	1.70	86.60	1.64	100.21	2.62	92.25	1.60
	High	108.36	1.36	85.35	2.18	86.82	4.50	101.30	2.29	95.38	1.13
23	Low	98.48	2.20	98.20	4.71	99.45	2.43	115.07	1.83	101.36	2.49
	Middle	92.04	3.17	97.55	1.59	97.30	2.67	115.97	2.57	89.46	2.43
	High	89.22	3.32	94.51	2.52	89.98	2.75	114.80	1.64	87.11	2.69

参考文献 26

[1]	Desai N, Albrecht E. Local anaesthetic adjuncts for peripheral nerve blockade[J]. Current Opinion in Anaesthesiology, 2023, 36(5): 533-540. doi: 10.1097/ACO.0000000000001272
[2]	Emeriewen K, McAuley W J, Beebeejaun M T, et al. The permeability of human eyelid skin to topically applied lidocaine[J]. Journal of Drug Delivery Science and Technology, 2020, 55: 101357.
[3]	Kim Y C, Castañeda A M, Lee C S, et al. Efficacy and safety of lidocaine infusion treatment for neuropathic pain: a randomized, double-blind, and placebo-controlled study[J]. Regional Anesthesia and Pain Medicine, 2018, 43(4): 415-424. doi: 10.1097/AAP.0000000000000741
[4]	Urfali S, Urfali B, Sarac E T, et al. Safety and complications of sedation anesthesia during pediatric auditory brainstem response testing[J]. ORL-Journal for Oto-Rhino-Laryngology Head and Neck Surgery, 2022, 84(3): 188-192.
[5]	Brazilian Society of Dermatology. Anais brasileiros de dermatologia[J]. Anais Brasileiros de Dermatologia, 2019, 94(1): 1-4. doi: 10.1016/S0365-0596(20)30287-7
[6]	Thai V T L, Nguyen T T, Ta Q H, et al. Impact of lidocaine concentration on analgesic efficacy and adverse events in dermatologic infiltrative anesthesia[J]. Dermatology Practical & Conceptual, 2025, 15(3): 5382.
[7]	Jiang S, Tang M. Allergy to local anesthetics is a rarity: review of diagnostics and strategies for clinical management[J]. Clinical Reviews in Allergy & Immunology, 2022, 64(2): 193-205.
[8]	Daikhin Y, Yudkoff M. Compartmentation of brain glutamate metabolism in neurons and glia[J]. The Journal of Nutrition, 2000, 130(4): 1026S-1031S.
[9]	Lai Luying, Wang Yongwei, Peng Shenghui, et al. Bupivacaine induces ROS-dependent autophagic damage in DRG neurons via TUG1/mTOR in a high-glucose environment[J]. Neurotoxicity Research, 2022, 40(1): 111-126. doi: 10.1007/s12640-021-00461-8 pmid: 35043378
[10]	De C A, Geraldini F, Costa F, et al. Local anesthetics and erector spinae plane blocks: a spotlight on pharmacokinetic considerations and toxicity risks[J]. Expert Opinion on Drug Metabolism & Toxicology, 2022, 18(9): 537-539.
[11]	Weissberg A, Drug E, Prihed H, et al. Structural elucidation of amino amide-type local anesthetic drugs and their main metabolites in urine by LC-MS after derivatization and its application for differentiation between positional isomers of prilocaine[J]. Journal of Mass Spectrometry, 2020, 55(10): e4654. doi: 10.1002/jms.v55.10
[12]	Liang Shanyan, Shi Fang, Zhao Yonggang, et al. Determination of local anesthetic drugs in human plasma using magnetic solid-phase extraction coupled with high-performance liquid chromatography[J]. Molecules, 2022, 27(17): 5509. doi: 10.3390/molecules27175509
[13]	Verdier N, Hummel K, Razzazi-Fazeli E, et al. A method for analysis of free and total ropivacaine in dog plasma using UHPLC-MS/MS[J]. Biomedical Chromatography, 2025, 39(10): e70214.
[14]	Alghamdi H, Alsaeedi M, Hayes P E, et al. Rapid and sensitive simultaneous separation and electrochemical detection of tetracaine hydrochloride and oxymetazoline hydrochloride in pharmaceutical formulations via core-shell reversed-phase liquid chromatography[J]. Journal of Pharmaceutical and Biomedical Analysis, 2022, 214: 114717.
[15]	Kaushal D, Lal H, Ansari S S, et al. Effect of local anesthetic drug procaine hydrochloride on the conformational stability of bovine hemoglobin: multi-spectroscopic and computational approaches[J]. Journal of Biomolecular Structure and Dynamics, 2022, 40(19): 8938-8948. doi: 10.1080/07391102.2021.1920465
[16]	Zhao Chaoyang, Ma Xinyue, Zang Jialin, et al. In situ enrichment and determination of 6 kinds of caine-type anesthetics in cosmetics and rat serum by thin layer chromatography-raman spectroscopy[J]. Arabian Journal of Chemistry, 2023, 16(10): 105121.
[17]	Jin Ying, He Chaoqun, Di Xiangjie, et al. Simultaneous determination of lidocaine and its active metabolites in plasma by UPLC-MS/MS and application to a clinical pharmacokinetic study in liver cancer patients with laparoscopic hepatectomy[J]. Journal of Chromatography B, 2022, 1207: 123362.
[18]	Mao Jie, Peng Jing, Zhu Yingjie, et al. Rapid UHPLC-MS/MS detection of prohibited drugs in cosmetics using pass-through SPE[J]. ACS Omega, 2025, 10(15): 15716-15724. doi: 10.1021/acsomega.5c01319
[19]	Zhang Liping, Shen Lingling, Zhong Qisheng, et al. Diluting modulation-based two dimensional-liquid chromatography coupled with mass spectrometry for simultaneously determining multiclass prohibited substances in cosmetics[J]. Journal of Chromatography A, 2023, 1695: 463954.
[20]	Laposchan S, Kranenburg R F, Van Asten A C. Impurities, adulterants and cutting agents in cocaine as potential candidates for retrospective mining of GC-MS data[J]. Science & Justice, 2022, 62(1): 60-75.
[21]	Jian Pengli, Muhammad T, Wei Aixia, et al. A membrane-protected micro-solid-phase extraction method based on molecular imprinting and its application to the determination of local anesthetics in cosmetics[J]. Journal of Separation Science, 2022, 45(14): 2675-2686. doi: 10.1002/jssc.202200012 pmid: 35544325
[22]	Pysarevska S, Plotycya S, Dubenska L. Voltammetry of local anesthetics: theoretical and practical aspects[J]. Critical Reviews in Analytical Chemistry, 2021, 51(4): 339-352. doi: 10.1080/10408347.2020.1729691
[23]	Ministry of Health of the People’s Republic of China. Hygienic standard for cosmetics: GB 7916—1987[S]. Beijing: China Standard Press, 1988.
[24]	Yang Jianying, Zhu Hong, Xu Ning, et al. Determination of 21 anesthetics in skin care products by QuEChERS/high performance liquid chromatography-tandem mass spectrometry[J]. Journal of Instrumental Analysis, 2023, 42(2): 189-196.
[25]	Lu Li, Fang Fang, Feng Youlong, et al. Determination of 16 caine-type ingredients in cosmetics by UPLC-QQQ/LIT tandem mass spectrometry coupled with solid phase extraction[J]. Journal of Pharmaceutical Analysis, 2021, 41(12): 2178-2190.
[26]	Lu Li, Fang Fang, Feng Youlong, et al. Determination of 15 caine-type prohibited ingredients in cosmetics by solid phase extraction-high performance liquid chromatography[J]. China Surfactant Detergent & Cosmetics, 2021, 51(8): 795-801.

No.	Compound name	Precursor ion（m/z）	R_t/min	Product ion（m/z）	DP/V	CE/V
1	Procaine	237.2	1.23	99.9^*	72	17
1	Procaine	237.2	1.23	119.8	23	41
2	Procainamide	236.2	1.81	162.1^*	91	34
2	Procainamide	236.2	1.81	119.9	65	62
3	Chloroprocaine	271.1	4.37	197.8^*	60	26
3	Chloroprocaine	271.1	4.37	153.2	84	50
4	Lidocaine	235.2	4.83	86.1^*	71	25
4	Lidocaine	235.2	4.83	58.0	38	27
5	Mepivacaine	247.1	4.93	98.1^*	71	23
5	Mepivacaine	247.1	4.93	70.1	84	63
6	Prilocaine	221.1	5.03	85.9^*	53	66
6	Prilocaine	221.1	5.03	135.8	20	28
7	Dezocine	246.2	5.75	146.9^*	63	28
7	Dezocine	246.2	5.75	229.0	66	15
8	Cocaine	304.1	6.11	181.8^*	77	43
8	Cocaine	304.1	6.11	82.0	71	47
9	Ropivacaine	275.3	6.11	126.1^*	91	30
9	Ropivacaine	275.3	6.11	84.0	93	62
10	Proxymetacaine	295.2	6.32	99.9^*	23	22
10	Proxymetacaine	295.2	6.32	135.9	107	35
11	Piperocaine	261.7	6.37	104.8^*	49	39
11	Piperocaine	261.7	6.37	162.9	43	29
12	Xylazole	204.6	6.52	188.6^*	88	39
12	Xylazole	204.6	6.52	104.7	97	32
13	Dyclonine	289.4	6.68	97.9^*	110	22
13	Dyclonine	289.4	6.68	140.0	75	27
14	Bupivacaine	289.2	6.68	98.1^*	81	51
14	Bupivacaine	289.2	6.68	140.2	87	27
15	Butacaine	307.2	6.78	177.9^*	107	27
15	Butacaine	307.2	6.78	119.8	129	61
16	Oxybuprocaine	309.2	6.78	235.9^*	64	26
16	Oxybuprocaine	309.2	6.78	191.8	109	26
17	Tetracaine	265.2	6.98	176.0^*	28	21
17	Tetracaine	265.2	6.98	71.9	60	41
18	Tricaine	165.8	6.98	137.9^*	62	20
18	Tricaine	165.8	6.98	93.9	66	29
19	Midazolam	326.1	6.98	291.0^*	125	39
19	Midazolam	326.1	6.98	249.1	88	50
20	Pramoxine	294.2	7.40	150.9^*	75	29
20	Pramoxine	294.2	7.40	99.7	134	50
21	Benzocaine	166.2	7.55	120.0^*	61	28
21	Benzocaine	166.2	7.55	94.0	59	23
22	Cinchocaine	344.0	7.60	270.9^*	91	34
22	Cinchocaine	344.0	7.60	215.1	108	45
23	Quinisocaine	273.4	7.91	72.0^*	62	27
23	Quinisocaine	273.4	7.91	227.9	26	24

Positive samples	Compound name	Detection value/（μg/g）				Average value/ （μg/g）	RSD/ %
Positive samples	Compound name	Screening Platform	Validating institution 1	Validating institution 2	Validating institution 3	Average value/ （μg/g）	RSD/ %
Sample 1	Dyclonine	2.512	2.666	2.586	2.623	2.563	4.28
Sample 1	Dyclonine	2.426	2.733	2.545	2.496	2.563	4.28
Sample 2	Lidocaine	2.647	2.580	2.560	2.421	2.537	4.74
Sample 2	Lidocaine	2.665	2.567	2.480	2.427	2.537	4.74