液相色谱-串联质谱法同时测定化妆品中40种抗菌药物

doi:10.3969/j.issn.1001-1803.2020.06.011

Abstract

Abstract:

A liquid chromatography-tandem mass spectrometry（LC-MS/MS） method for the simultaneous determination of 40 antibacterial agents including tetracycline, metronidazole, ofloxacin and sulfapyridine in cosmetics was established. The samples were extracted with 20% acetonitrile （containing 0.5% formic acid） as the extraction solvent. The LC part used 0.5% formic acid aqueous solution as the mobile phase A and 0.5% formic acid in acetonitrile solution as the mobile phase B, gradient elution, the injection volume was 2 μL, the flow rate was 0.3 mL/min, and the column temperature was 30 ℃. The MS part was determined by electrospray ion source, positive ion multiple reaction monitoring mode （MRM）, and the external standard method was used for quantitative analysis. The results show that the linear range of 40 antibiotics was within 20-100 μg/L, the correlation coefficient was more than 0.997, and the detection limit was within 0.025-0.25 μg/g. The average recovery rate of 40 antibiotics was 73.8%-109.1% at the low, medium and high spiked mass concentrations. Among the 84 batches of samples screened, 1 batch of samples detected metronidazole, 1 batch of samples detected ciprofloxacin, and 1 batch of samples detected metronidazole and ofloxacin. The method has good selectivity, sensitivity and accuracy, and can be used for the simultaneous determination of 40 illegally added antibacterial agents in cosmetics.

Key words: LC-MS/MS, cosmetic, antibiotics, external standard method

CLC Number:

TQ658

XIAO Rui-na,LI Yu-li. Simultaneous determination of 40 antibacterial agents in cosmetics by liquid chromatography tandem mass spectrometry[J].China Surfactant Detergent & Cosmetics, 2020, 50(6): 419-426.

Figures/Tables 7

Tab. 1

Tab. 2

Mass spectrometry parameters of 40 antibiotics"

编号	化合物	分子式	保留时间/min	母离子（m/z）	DP电压/V	子离子1（m/z）	碰撞能量1（E₁）/eV	子离子2（m/z）	碰撞能量2（E₂）/eV
1	四环素	C₂₂H₂₄N₂O₈	7.2	445.1	50	410.2^*	26	427.2	17
2	金霉素	C₂₂H₂₃ClN₂O₈	8.88	479.1	60	444.2^*	27	462.2	23
3	土霉素	C₂₂H₂₄N₂O₉	7.34	461.1	80	426.2 ^*	23	443.2	17
4	多西环素	C₂₂H₂₄N₂O₈	8.97	445.1	40	428.2 ^*	23	410.2	27
5	米诺环素	C₂₃H₂₇N₃O₇	4.38	458.2	75	441.3 ^*	23	352.1	38
6	加替沙星	C₁₉H₂₂FN₃O₄	8.44	376.1	68	332.2 ^*	23	358.2	28
7	氟罗沙星	C₁₇H₁₈F₃N₃O₃	7.05	370.0	54	326.2 ^*	27	269.0	38
8	氧氟沙星	C₁₈H₂₀FN₃O₄	6.75	362.0	34	318.2 ^*	27	261.2	38
9	依诺沙星	C₁₅H₁₇FN₄O₃	6.19	321.0	80	234.2 ^*	29	277.2	22
10	培氟沙星	C₁₇H₂₀FN₃O₃	6.93	334.1	80	290.2 ^*	24	316.2	29
11	诺氟沙星	C₁₆H₁₈FN₃O₃	6.66	320.1	50	276.2 ^*	23	233.1	33
12	环丙沙星	C₁₇H₁₈FN₃O₃	7.06	332.0	100	288.2 ^*	25	314.2	28
13	恩诺沙星	C₁₉H₂₂FN₃O₃	8.16	360.0	116	316.2 ^*	25	342.2	29
14	双氟沙星	C₂₁H₁₉F₂N₃O₃	8.63	400.1	80	356.2 ^*	28	382.2	28
15	沙拉沙星	C₂₀H₁₇F₂N₃O₃	8.59	386.1	98	342.2 ^*	25	299.1	39
16	莫西沙星	C₂₁H₂₄FN₃O₄	8.67	402.1	96	384.2 ^*	29	358.2	28
17	司帕沙星	C₁₉H₂₂F₂N₄O₃	8.59	393.0	78	349.2 ^*	26	292.2	34
18	帕珠沙星	C₁₆H₁₅FN₂O₄	6.58	319.0	72	302.1 ^*	14	281.2	34
19	甲硝唑	C₆H₉N₃O₃	7.79	172.1	64	128.0 ^*	19	82.0	34
20	氟康唑	C₁₃H₁₂F₂N₆O	9.68	307.0	65	220.1 ^*	25	238.1	24
21	灰黄霉素	C₁₇H₁₇ClO₆	13.67	353.0	60	165.1 ^*	24	215.0	24
22	酮康唑	C₂₆H₂₈Cl₂N₄O₄	9.27	531.2	130	255.2 ^*	45	489.3	44
23	萘替芬	C₂₁H₂₁N	9.66	288.1	46	117.0 ^*	25	141.1	34
24	克霉唑	C₂₂H₁₇ClN₂	9.86	277.0	130	165.1 ^*	34	241.2	34
25	咪康唑	C₁₈H₁₄Cl₄N₂O	10.60	417.0	100	159.0 ^*	39	161.0	39
26	益康唑	C₁₈H₁₅Cl₃N₂O	10.26	381.0	84	125.1 ^*	35	193.3	26
27	联苯苄唑	C₂₂H₁₈N₂	9.89	311.2	80	243.2 ^*	14	165.1	44
28	呋喃他酮	C₁₃H₁₆N₄O₆	6.21	325.1	67	252.1 ^*	20	281.2	15
29	磺胺吡啶	C₁₁H₁₁N₃O₂S	9.38	250.0	66	156.1 ^*	22	92.0	35
30	磺胺甲嘧啶	C₁₁H₁₂N₄O₂S	9.82	265.0	90	155.9 ^*	22	172.1	20
31	磺胺甲二唑	C₉H₁₀N₄O₂S₂	9.98	271.0	40	92.0 ^*	35	156.0	19
32	磺胺甲氧嗪	C₁₁H₁₂N₄O₃S	10.01	281.0	60	155.9 ^*	22	92.0	35
33	磺胺氯哒嗪	C₁₀H₉ClN₄O₂S	10.93	285.0	90	156.0 ^*	19	92.0	35
34	磺胺甲噁唑	C₁₀H₁₁N₃O₃S	11.20	254.0	60	92.0 ^*	35	156.0	20
35	罗红霉素	C₄₁H₇₆N₂O₁₅	9.59	837.6	60	679.5 ^*	27	558.4	32
36	头孢克肟	C₁₆H₁₅N₅O₇S₂	8.85	454.0	70	285.1 ^*	20	210.1	26
37	林可霉素	C₁₈H₃₄N₂O₆S	5.15	407.1	90	126.1 ^*	34	359.3	26
38	克林霉素	C₁₈H₃₃ClN₂O₅S	8.79	425.1	100	126.0 ^*	35	377.2	26
39	头孢拉定	C₁₆H₁₉N₃O₄S	7.36	350.1	84	158.0 ^*	15	176.3	16
40	头孢他啶	C₂₂H₂₂N₆O₇S₂	4.73	547.2	100	468.1 ^*	16	396.2	21

Tab. 2

Tab. 3

Summary of linear range, correlation coefficient, detection limit and limit of quantitation of 40 antibiotics"

编号	化合物	回归方程	相关系数R	检出限/（μg·g^-1）	定量限/（μg·g^-1）
1	四环素	y=4 415.2x-12 466.1	0.999 6	0.25	0.75
2	金霉素	y=3 087.0x-4 463.0	0.999 1	0.19	0.56
3	土霉素	y=8 463.4x-9 867.4	0.999 1	0.25	0.75
4	盐酸多西环素	y=16 574.2x-49 219.3	0.999 0	0.25	0.75
5	米诺环素	y=3 409.1x-13 122.0	0.999 4	0.19	0.56
6	加替沙星	y =13 199.1x-9 672.5	0.999 4	0.025	0.075
7	氟罗沙星	y=20 901.9x-15 359.9	0.998 3	0.025	0.075
8	氧氟沙星	y=37 817.3x-20 483.2	0.999 1	0.025	0.075
9	依诺沙星	y=3 779.9x-3 428.0	0.999 2	0.025	0.075
10	培氟沙星	y=10 650.6x-12 304.1	0.999 2	0.025	0.075
11	诺氟沙星	y=6 793.8x-10 740.3	0.999 2	0.025	0.075
12	环丙沙星	y=6 459.1x-9 189.1	0.999 2	0.025	0.075
13	恩诺沙星	y=17 281.9x-36 809.4	0.999 2	0.075	0.22
14	双氟沙星	y=11 789.9x-11 294.9	0.999 0	0.025	0.075
15	沙拉沙星	y=7 477.4x-9 400.1	0.999 1	0.075	0.22
16	莫西沙星	y=21 114.5x-84 379.4	0.999 1	0.025	0.075
17	司帕沙星	y=26 389.3x-16 497.3	0.999 3	0.025	0.075
18	帕珠沙星	y=6 622.7x-8 056.1	0.999 4	0.025	0.075
19	甲硝唑	y=7 600.7x+18 446.8	0.999 1	0.25	0.75
20	氟康唑	y=15 864.8x+8 882.6	0.999 4	0.025	0.075
21	灰黄霉素	y=13 026.9x+61 038.6	0.999 1	0.075	0.22
22	酮康唑	y=789.0x-1 940.7	0.999 0	0.19	0.56
23	萘替芬	y=80 209.3x-33 196.90	0.999 4	0.05	0.15
24	克霉唑	y=110 599.0x-145 021.0	0.999 3	0.05	0.15
25	咪康唑	y=33 932.5x-23 065.3	0.999 4	0.075	0.22
26	益康唑	y=68 948.7x-18 419.9	0.999 1	0.025	0.075
27	联苯苄唑	y=99 005.9x-94 927.7	0.999 1	0.075	0.22
28	呋喃它酮	y=24 797.0x-40 401.3	0.999 5	0.075	0.22
29	磺胺吡啶	y=33 012.3x+27 269.4	0.999 4	0.075	0.22
30	磺胺甲嘧啶	y=27 242.1x-7 406.9	0.999 3	0.075	0.22
31	磺胺甲二唑	y=10 098.8x+9 934.8	0.999 4	0.25	0.75
32	磺胺甲氧嗪	y=38 374.9x-3 189.2	0.999 7	0.075	0.22
33	磺胺氯哒嗪	y=13 656.8x+35 007.4	0.999 4	0.075	0.22
34	磺胺甲噁唑	y=9 968.6x+24 799.8	0.999 4	0.05	0.15
35	罗红霉素	y=23 380.7x-56 023.7	0.999 3	0.075	0.225
36	头孢克肟	y=4 163.1x-4 664.1	0.999 3	0.025	0.075
37	林可霉素	y=106 660.0x-146 935.0	0.999 2	0.075	0.22
38	克林霉素	y=44 646.1x-87 882.8	0.999 0	0.025	0.075
39	头孢拉啶	y=2 372.1x+32 066.1	0.997 4	0.025	0.075
40	头孢他啶	y=941.0x-2 690.2	0.999 1	0.25	0.75

Tab. 3

Tab. 4

Recovery and precision of 40 antibiotics （n=6）"

编号	化合物	平均回收率/%			RSD/%
编号	化合物	1组	2组	3组	1组	2组	3组
1	四环素	79.0	82.9	80.4	9.5	6.0	7.8
2	金霉素	84.0	95.9	93.9	6.2	5.1	4.6
3	土霉素	89.7	84.5	86.2	6.3	7.1	9.4
4	盐酸多西环素	90.9	95.7	96.2	5.1	6.6	1.3
5	米诺环素	79.3	81.0	96.7	9.9	8.7	1.8
6	加替沙星	77.9	94.4	99.3	6.3	4.7	9.1
7	氟罗沙星	82.6	90.6	90.6	4.7	7.2	7.4
8	氧氟沙星	85.2	83.2	85.9	9.2	8.9	8.6
9	依诺沙星	87.2	93.4	95.3	8.8	7.7	9.0
10	培氟沙星	86.0	91.8	97.2	8.2	5.5	10.8
11	诺氟沙星	87.1	96.5	91.8	7.4	1.7	7.7
12	环丙沙星	90.1	97.1	90.5	9.3	7.4	9.8
13	恩诺沙星	93.0	87.6	92.9	9.2	10.0	8.9
14	双氟沙星	84.5	100.1	97.3	3.3	4.1	4.1
15	沙拉沙星	88.4	102.5	101.9	6.5	3.3	3.1
16	莫西沙星	105.7	95.0	90.7	3.1	9.1	2.0
17	司帕沙星	82.9	98.8	100.0	2.8	3.5	2.9
18	帕珠沙星	81.3	96.0	97.5	6.4	6.6	8.3
19	甲硝唑	91.5	90.7	91.8	2.4	7.0	5.5
20	氟康唑	78.4	95.1	102.2	8.2	7.2	6.9
21	灰黄霉素	82.3	80.0	91.0	6.7	3.0	6.6
22	酮康唑	87.0	85.2	83.3	10.4	8.8	6.2
23	萘替芬	74.2	89.0	92.4	7.7	5.7	7.2
24	克霉唑	82.7	97.2	94.1	3.3	6.4	3.0
25	咪康唑	88.9	91.7	109.1	8.1	5.1	3.4
26	益康唑	86.8	94.9	97.2	2.0	4.9	3.7
27	联苯苄唑	86.8	98.1	99.2	5.5	7.4	1.4
28	呋喃它酮	78.1	85.7	82.0	6.2	10.2	6.4
29	磺胺吡啶	79.9	79.9	87.6	3.6	8.3	7.3
30	磺胺甲嘧啶	76.5	92.3	85.7	7.4	6.6	1.9
31	磺胺甲二唑	94.2	89.5	87.6	2.1	11.5	4.5
32	磺胺甲氧嗪	87.5	83.7	87.2	2.4	4.9	4.0
33	磺胺氯哒嗪	81.7	91.2	93.9	3.1	3.8	3.2
34	磺胺甲噁唑	82.8	85.4	91.0	2.7	2.9	2.6
35	罗红霉素	92.3	104.9	95.4	8.8	12.4	11.1
36	头孢克肟	81.0	92.2	93.0	7.1	6.2	2.6
37	林可霉素	87.9	99.8	84.1	1.9	7.7	4.2
38	克林霉素	86.3	94.3	95.2	3.8	4.3	3.9
39	头孢拉啶	82.6	93.7	92.6	4.8	9.1	5.2
40	头孢他啶	87.4	101.2	88.7	3.9	5.2	1.9

Tab. 4

Fig. 1

Tab. 5

Fig. 2

References 10

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	甲硝唑含量/（μg·g^-1）		环丙沙星含量/（μg·g^-1）		氧氟沙星含量/（μg·g^-1）
	本方法	《化妆品安全技术规范》（2015年版）方法	本方法	《化妆品安全技术规范》（2015年版）方法	本方法	《化妆品安全技术规范》（2015年版）方法
样品1	7 746	6 707	/	/	/	/
样品2	/	/	8 685	8 348	/	/
样品3	4 161	3 623	/	/	3 253	3 674

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Simultaneous determination of 40 antibacterial agents in cosmetics by liquid chromatography tandem mass spectrometry

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