Xiaoqing Zhou, Man He, Beibei Chen, Bin Hu
*
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education),
Department of Chemistry, Wuhan University, Wuhan 430072, China
Supplemental materials
Fig. S1 (A) The scheme of MS-LLLME. (B) The home-made porous nylon membrane supported extraction tip. (C) Photographs of MS-LLLME. The picture was from Ref. [22].
* Corresponding author. Tel.: +86 27 68752162; Fax: +86 27 68754067.
E-mail address: binhu@whu.edu.cn (B. Hu)

Fig. S2 Effect of the content of CH
3
OH in BGE on the separation of target analytes
(50 mbar for 2 s).
40
35
30
25
20
15
10
5
0
1
6
2
3
456 7
0 CH
R
5,6
3
OH
=0.80
8
Time/ min
1: mexiletine
2: xylocaine
3: propranolol
4: metoprolol
5: propafenone
6: carvedilol
7: labetalol 5% CH
3
OH
R
5,6
=1.23
10% CH
3
OH
R
5,6
=2.78
15% CH
3
OH
R
5,6
=3.75
10 12

Fig.S3 Effect of different organic solvents on MS-LLLME. Conditions: donor phase: 9 mL 0.1 mol
L
-1
NaOH sample solution spiked with 200 µg L
-1
of each analytes and without salt addition, acceptor phase: 50 mmol L
-1
HAc, stirring rate: 500 rpm, extraction time: 40 min.
120
100
80
60
mexiletine
xylocaine
propranolol
metoprolol
propafenone
carvediol
40
20
0 toluene:n-octanol (1:1) phenetole decane
Different organic solvents toluene

Fig. S4 Effect of the concentration of NaOH on MS-LLLME. Conditions: donor phase: 9 mL sample solution without salt addition, acceptor phase: 50 mmol L
-1
HAc, stirring rate: 500 rpm, extraction time: 40 min, sample concentration: 200 µg L
-1
.
140
120
mexiletine
xylocaine
propranolol
metoprolo
propafenone
carvedilol
100
80
60
40
20
0
0.0
0.1
0.2
0.3
0.4
Concentration of NaOH (mol L
-1
)
0.5

Fig. S5 Effect of the concentration of HAc on MS-LLLME. Conditions: donor phase: 9 mL 0.1 mol
L
-1
NaOH sample solution spiked with 200 µg L
-1
of each analytes and without salt addition, stirring rate: 500 rpm, extraction time: 40 min.
mexiletine
xylocaine
propranolol
metoprolol
propafenone
carvedilol
160
140
120
100
80
60
40
20
0
0 20 40 60 80 100 120
Concentration of HAc (mmol L
-1
)
140 160

Fig. S6 Effect of the extraction time on MS-LLLME. Conditions: donor phase: 9 mL 0.1 mol L
-1
NaOH sample solution spiked with 200 µg L
-1
of each analytes and without salt addition, acceptor phase: 20 mmol L
-1
HAc, stirring rate: 600 rpm.
200
180
160
140
120
100
80
60
40
20
0
10
mexiletine
xylcoine
propranolol
metoprolol
propafenone
carvedilol
20 30 40
Extraction time/ min
50 60

Fig. S7 Effect of the multiple dilution of urine sample on MS-LLLME-FASI-CE-UV. Conditions: donor phase: 9 mL 0.1 mol L
-1
NaOH sample solution spiked with 40 µg L
-1
of each analytes, acceptor phase: 20 mmol L
-1
HAc, stirring rate: 600 rpm, extraction time: 50 min, water plug: 50 mbar for 3 s, injection voltage/time: +6 kV for 18 s.
1500
1200
900
600
300
mexiletine
xylocaine
propranolol
metoprolol
propafenone carvedilol
0
0-fold 5-fold 15-fold 25-fold 50-fold 100-fold pure water
Effect of multiple dilution of urine

Analytes
Carvedilol
Metoprolol
Table S1 Structures, log P values and p Ka of the target analytes
Structures Log P
4.074 p Ka
13.90 (acidic)
8.24 (basic)
13.89
9.43
Propranolol
Xylocaine
Mexiletine
Propafenone
1.632
2.900
2.196
2.124
3.351
13.84
9.50
14.23
7.96
8.58
13.82
9.31

Table S2 Stacking efficiency obtained with and without water plug mexiletine xylocaine propranolol metoprolol propafenone carvedilol Analyte
A
B(n ± SD)
C(n ± SD)
B/A
C/A
28.3 26.3 24.8 22.6 15.5 18.7
614.9
± 64.7 468.6
± 58.1 435.2
± 58.0 311.0
± 44.1 256.9
± 38.3 388.9
± 57.9
718.4
± 16.1 560.7
± 16.5 522.6
± 16.7 383.2
± 14.2 309.9
± 9.6
21.7
25.3
17.8
21.3
17.5
21.0
13.7
16.9
16.5
19.9
469.6
± 17.1
20.7
25.1
A: The peaks area obtained by standard injecting of 10 µg/mL analytes (50 mbar 5 s, without any concentration techniques);
B: The peaks area obtained by injecting of 10 µg/mL analytes using FASI method without water plug;
C: The peaks area obtained by injecting of 10 µg/mL analytes using FASI method with water plug (50 mbar 3 s);
B/A: the ratio of B and A;
C/A: the ratio of C and A.