Review Article

The Use of Dried Blood Spots for the Quantification of Antihypertensive Drugs

Table 1

Published DBS sampling techniques for analysis of antihypertensive medications and statins.

Drug analyzedDBS card/paper usedDiameter of disk punched for analysis, mmCalibration range, ng/mLStability of DBS samplesElution procedure (min)V, Extraction solventRecovery (%)Mass-spectrometerDetection modeMass or transmission,
m/z
Internal standardRef.

Angiotensin converting enzyme inhibitors

RamiprilWhatman 90380.5 - 10084 days, RTmixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)≥92Agilent G6530A QTOFTOF417.2384Atenolol[48]
Whatman 9038-84 days, RTmixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)-Agilent 6530 QTOFTOF417.2384Atenolol[49]
Whatman 90380.1 - 10070 days, RTmixed (1 min) + sonicated (30 min)300 μL, MeOH≥87Agilent G6530A QTOFTOF417.2384Atenolol-d7[50]
Ahlstrom 2268See [48]-mixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)See [48]Agilent G6530A QTOFTOF417.2384Atenolol[51]

RamiprilatWhatman 903Whole DBS5 - 25021 days, 25°C
21 days, 37°C
21 days,-20°C
mixed (1 min) + sonicated (10 min) + mixed (45 min)300 μL, MeOH/0.1% FA (90:10, v/v)65-81Agilent 6460 QQQMRM389.2 → 206.1Ramiprilat-d5[52]
Ahlstrom 2268See [48]-mixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)See [48]Agilent G6530A QTOFTOF389.2071Atenolol[51]

CaptoprilWhatman 903810 - 40084 days, RTmixed (1 min) + sonicated (30 min)200 μL, MeOH/H2O (60:40, v/v) with 10% v/v 200 mM DTT90 ± 10Agilent 1100 Ion Trap
Agilent 6530 TOF
SRM
TOF
218.0
218.0845
Enalapril maleate[53]

LisinoprilWhatman 90380.1 - 10070 days, RTmixed (1 min) + sonicated (30 min)300 μL, MeOH≥87Agilent G6530A QTOFTOF406.2336Atenolol-d7[50]

Angiotensin II receptor antagonists

ValsartanWhatman 903850 - 400070 days, RTmixed (1 min) + sonicated (30 min)300 μL MeOH≥87Agilent G6530A QTOFTOF436.2343Atenolol-d7[50]
Whatman 9038-84 days, RTmixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)-Agilent 6530 QTOFTOF436.2343Atenolol[49]
Whatman DMPK-A106 - 200030 days, RTmixed (15 min)1000 μL, MeOH98-fluorescence--[54]

IrbesartanWhatman 90332030 days, RTmixed (5 min) + sonicated (10 min)500 μL, MeOH/H2O (50:50, v/v)Agilent 1100 Ion TrapMRM427.3 → 193.0Irbesartan[55]
Whatman DMPK-A106 - 200030 days, RTmixed (15 min)1000 μL, MeOH99-fluorescence--[54]

LosartanWhatman 90385 - 100070 days, RTmixed (1 min) + sonicated (30 min)300 μL, MeOH≥87Agilent G6530A QTOFTOF423.1695Atenolol-d7[50]
Whatman 90331 - 20030 days, RTmixed (5 min) + sonicated (10 min)500 μL, MeOH/H2O (50:50, v/v)89-94Agilent 1100 Ion TrapMRM421.2 → 179.0Irbesartan[55]
Whatman DMPK-A1012 - 400030 days, RTmixed (15 min)1000 μL, MeOH98-fluorescence--[54]

Losartan carboxylic acidWhatman 90335 - 100030 days, RTmixed (5 min) + sonicated (10 min)500 μL, MeOH/H2O (50:50, v/v)93-98Agilent 1100 Ion TrapMRM421.2 → 179.0Irbesartan[55]

Calcium channel blockers

VerapamilWhatman 903
Whatman DMPK-C
Ahlstrom 237
Whatman DMPK-A
Whatman DMPK-B
3500mixed (60 min)200 μL, ACN/H2O (75:25, v/v)AB Sciex API 4000SRM455 → 165Verapamil[56]
Whatman DMPK-C2 1 - 1000Used SPE cartridge1000 μL, 0.2% FA in H2O81AB Sciex API 4000MRM455.3→ 165.2Imipramine[57]
Whatman filter paper, Grade CF 12Whole DBS50 - 500-On-line desorption100% ACN-Agilent 1100 MSD single Q VL versionSRM-Trimipramine-d3[58]
Whatman grade SG81 ion exchange paperWhole DBS0.01 - 10000-Paper sprayMeCl2/isopropanol
(90:10, v/v)
-Thermo TSQ Quantum Access Max QQQSRM455 → 303-[59]

AmlodipineWhatman 9038-84 days, RTmixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)-Agilent 6530 QTOFTOF431.1344Atenolol[49]

NifedipineAhlstrom 226410 - 100001 day, RT-200 μL, ACN/H2O
(75:25, v/v)
-AB Sciex API 4000MRM347→ 315[13C,15N2]-nifedipine nitrophenyl pyridine[60]

PregabalinWhatman 9034200 - 20000120 days, 4°Cmixed (10 min) + Derivatization100 μL, 0.1 mol/L HCl98-102Thermo TSQ Quantum Access MAX QQQSRM288.0 → 142.1
288.0 → 228.0
4-aminocyclohexanecarboxylic acid[61]

DiltiazemWhatman 90380.5 - 60070 days, RTmixed (1 min) + sonicated (30 min)300 μL, MeOH≥87Agilent G6530A QTOFTOF415.1686Atenolol-d7[50]

blockers

GuanfacineWhatman DMPK-C50.05 - 2576 days, RTmixed (10 min)600 μL, TBME~80AB SCIEX 5500 QTRAPSRM246.1→ 60.1[13C,15N3]-guanfacine hydrochloride[62]
Whatman DMPK-C4 0.01 - 25-On-line DBS-SPE system1000 μL, ACN/0.1% FA (80:20, v/v) + 1000 μL, 0.1% FA-AB SCIEX 5500 QTRAPSRM246.1 → 60.1[13C,15N3]-guanfacine hydrochloride[63]
two-layered polymeric membrane2 0.25 - 250-On-line DBS-SPE system1000 μL, ACN/0.1% FA (80:20, v/v) + 1000 μL, 0.1% FA-AB SCIEX 5500 QTRAPSRM246.1 → 60.1[13C,15N3]-guanfacine hydrochloride[64]

DoxazosinWhatman 9038-84 days, RTmixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)-Agilent 6530 QTOFTOF452.1928Atenolol[49]
Whatman 90380.1 - 10070 days, RTmixed (1 min) + sonicated (30 min)300 μL, MeOH≥87Agilent G6530A QTOFTOF452.1928Atenolol-d7[50]

PrazosinWhatman 903
Whatman DMPK-C
Ahlstrom 237
Whatman DMPK-A
Whatman DMPK-B
3100 - 10000-mixed (60 min) + sonicated (30 min)200 μL, ACN/H2O (75:25, v/v) or
MeOH for DMPK-B
-AB Sciex API 4000SRM384 → 247Verapamil[56]

blockers

PropranololWhatman 903Whole DBS5 - 25021 days, 25°C
21 days, 37°C
21 days,-20°C
mixed (1 min) + sonicated (10 min)+ mixed (45 min)300 μL, MeOH/0.1% FA (90:10, v/v)91-99Agilent 6460 QQQMRM260.2 → 116.1Propranolol-d7[52]
Whatman 9033.22.5 - 20030 days, RT
30 days, 4°C
30 days,-20°C
mixed (25 min)200 μL, MeOH/0.1% FA (95:5, v/v)94-100AB SCIEX 5500 QTRAPMRM260.1 → 116.1Propranolol-d7[65]
Whatman DMPK-C2 1 - 1000-Used SPE cartridge1000 μL, 0.2% FA in H2O83AB Sciex API 4000MRM260.1→ 116.1Imipramine[57]
Sartorius TFN, Munktell TFN, Whatman DMPK-CWhole DBS0 - 207 days, 4°Csonicated (45 + 30 min)100 μL, MeOH + 400 μL, TBME + 300 μL, acetone71Thermo Q Exactivescan-to-scan260.1645Cocaine-d3[66]
Watman DMPK-B31 - 500-mixed (10 min)300 μL, MeOH-AB Sciex API 4000MRM-Propranolol-d3[67]
Whatman filter paper4 1 - 500-Heating25 μL, MeOH with 0.1% FA70–82AB SCIEX 3200 QTRAPMRM260 → 183Propranolol-d7[68]

BisoprololWhatman 90380.1 - 10070 days, RTmixed (1 min) + sonicated (30 min)300 μL, MeOH≥87Agilent G6530A QTOFTOF326.2326Atenolol-d7[50]
Whatman 90380.1 - 10084 days, RTmixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)≥92Agilent G6530A QTOFTOF326.2326Atenolol[48]
Whatman 9038-84 days, RTmixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)~98Agilent 6530 QTOFTOF326.2326Atenolol[49]
Whatman 903Whole DBS5 - 25021 days, 25°C
21 days, 37°C
21 days,-20°C
mixed (1 min) + sonicated (10 min)+ mixed (45 min)300 μL, MeOH/0.1% FA (90:10, v/v)74-83Agilent 6460 QQQMRM326.2 → 116.1Bisoprolol-d5[52]
Sartorius TFN, Munktell TFN, Whatman DMPK-CWhole DBS0 - 207 days, 4°Csonicated (45 + 30 min)100 μL, MeOH + 400 μL, TBME + 300 μL, acetone60Thermo Q Exactivescan-to-scan326.2326Cocaine-d3[66]
Ahlstrom 2268See [48]See [48]mixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)See [48]Agilent G6530A QTOFTOF326.2326Atenolol[51]

AtenololWhatman 9038-84 days, RTmixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)-Agilent 6530 QTOFTOF267.1703Atenolol[49]
Whatman 903810 - 150070 days, RTmixed (1 min) + sonicated (30 min)300 μL, MeOH≥87Agilent G6530A QTOFTOF267.1703Atenolol-d7[50]
Whatman 903525 - 150070 days, 25°Cmixed (1 min) + sonicated (30 min)200 μL, MeOH/H2O (60:40, v/v)96-100Agilent 6530 QTOFTOF267.1703Atenolol-d7[29]

MetoprololWhatman DMPK-A52.5 - 250014 days, RTmixed (3 min)200 μL, 2% ammonium hydroxide + 700 μL, ethyl acetate77-86AB Sciex API 5000MRM268.2 → 116.2Metoprolol-d7[69]
Sartorius TFN, Munktell TFN, Whatman DMPK-CWhole DBS0 - 207 days, 4°Csonicated (45 + 30 min)100 μL, MeOH + 400 μL, TBME + 300 μL, acetone68Thermo Q Exactivescan-to-scan268.1907Cocaine-d3[66]

Endothelin receptor antagonists

BosentanWhatman DMPK-A-2 - 1500105 days, RTUsed Sample Card And Prep DBS SystemMeOH/H2O (50:50, v/v)83-92AB Sciex API 4000MRM552.2 → 202.1Bosentan-d4[70]
Whatman DMPK-A-2 - 3000105 days, RTUsed Sample Card And Prep DBS SystemMeOH/H2O (50:50, v/v)83-92AB Sciex API 4000MRM552.2 → 202.1Bosentan-d4[71]
Whatman DMPK-C6.22.5 - 4000147 days, RT
14 days, 37°C
14 days,-20°C
sonicated (20 min) + mixed (20 min)400 μL, H2O + 4000 μL, TBME69-83Thermo TSQ7000 QQQMRM552.4 → 202.1Bosentan-d4[72]

AmbrisentanWhatman DMPK-C6.22.5 - 1000147 days, RT
14 days, 37°C
14 days,-20°C
sonicated (20 min) + mixed (20 min)400 μL, H2O + 4000 μL, TBME88-94Thermo TSQ7000 QQQMRM347.3 → 125Ambrisentan-d10[72]

Statins

SimvastatinWhatman 90381 - 10084 days, RTmixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)~43Agilent G6530A QTOFTOF441.261 Na adductAtenolol[48]
Whatman 90380.1 - 10070 days, RTmixed (1 min) + sonicated (30 min)300 μL, MeOH68Agilent G6530A QTOFTOF441.2611Atenolol-d7[50]
Whatman 9038-84 days, RTmixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)~40Agilent 6530 QTOFTOF441.2611Atenolol[49]
Ahlstrom 2268See [70]See [70]mixed (1 min) + sonicated (30 min)150 μL, MeOH/H2O (70:30, v/v)See [70]Agilent G6530A QTOFTOF418.2719 / 441.2611 NA adductAtenolol[51]

AtorvastatinWhatman 90380.5 - 10070 days, RTmixed (1 min) + sonicated (30 min)300 μL, MeOH≥87Agilent G6530A QTOFTOF559.2610Atenolol-d7[50]

RosuvastatinWhatman DMPK- B30.5 - 80mixed (60 min)100 μL, MeOHWaters Xevo TQ-S QQQMRM482 → 258Rosuvastatin-d6[73]

ACN: acetonitrile, FA: formic acid, DTT: dithiothreitol, MeCl2: dichloromethane, MeOH: methanol, MSX: multiplex targeted SRM mode, and TBME: tert-butyl methyl ether.
: elution area