Do concentrations of pharmaceuticals in sewage reflect prescription figures?

Alexander L.N. van Nuijsa*, Adrian Covacia, Herman Beyersb, Lieven Bervoetsc, Ronny Blustc, Gert Verpootend, Hugo Neelsa,e, Philippe G. Jorense

a - Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp (UA), Universiteitsplein 1, 2610 Antwerp, Belgium

b - National Institute for Health and Disability Insurance (RIZIV), Tervurenlaan 211, 1150 Brussels, Belgium

c - Systemic Physiological and Ecotoxicological Research, Department of Biology, University of Antwerp (UA), Groenenborgerlaan 171, 2020 Antwerp, Belgium

d - Nephrology, Laboratory of Experimental Medicine and Pediatrics, University of Antwerp (UA), Universiteitsplein 1, 2610 Antwerp, Belgium

e - Laboratory of Toxicology, ZNA Stuivenberg, Lange Beeldekensstraat 267, 2060, Antwerp, Belgium

f - Department of Clinical Pharmacology/Clinical Toxicology, University of Antwerp (UA),Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium

*- corresponding author:

Dr. Alexander van Nuijs
Toxicological Centre, University of Antwerp
Universiteitsplein 1
2610 Wilrijk, Belgium
e-mail:
tel: +32 (0)3 265 24 98

Table SI1. Linearity, lower limit of quantification (LLOQ) and recovery results for the developed HILIC-MS/MS method. ATE: atenolol; BIS: bisoprolol; CIT: citalopram; MFM: metformin; TRA: tramadol; VEN: venlafaxine. SD = standard deviation; QC = quality control; SW = surface water; WW = wastewater

Pharma-
ceutical / Range (ng/L) / r² / LLOQ
(ng/L) / Within-run accuracy
(% (SD)) / Between-run accuracy
(% (SD)) / Within-run precision
(% RSD) / Between-run precision
(% RSD) / Extraction recovery
(% (SD))
QC
low
(n = 6) / QC
medium
(n = 6) / QC
high
(n = 6) / QC
low
(n = 21) / QC
medium
(n = 21) / QC
high
(n = 21) / QC
low
(n = 6) / QC
medium
(n = 6) / QC
high
(n = 6) / QC
low
(n = 21) / QC
medium
(n = 21) / QC
high
(n = 21) / SW
(n = 6) / WW
(n = 6)
ATE / 20-3 500 / 0.9988 / 20 / 108 (5) / 106 (6) / 100 (4) / 107 (7) / 108 (5) / 106 (6) / 100 (4) / 107 (7) / 108 (5) / 106 (6) / 100 (4) / 107 (7) / 101 (1) / 101 (8)
BIS / 1-360 / 0.9983 / 1 / 107 (4) / 94 (2) / 93 (5) / 102 (7) / 107 (4) / 94 (2) / 93 (5) / 102 (7) / 107 (4) / 94 (2) / 93 (5) / 102 (7) / 100 (2) / 100 (4)
CIT / 4-360 / 0.9954 / 4 / 112 (7) / 93 (3) / 97 (5) / 102 (10) / 112 (7) / 93 (3) / 97 (5) / 102 (10) / 112 (7) / 93 (3) / 97 (5) / 102 (10) / 96 (4) / 93 (2)
MFM / 500-120 000 / 0.9990 / 500 / 100 (4) / 100 (3) / 102 (2) / 98 (5) / 100 (4) / 100 (3) / 102 (2) / 98 (5) / 100 (4) / 100 (3) / 102 (2) / 98 (5) / 21 (3) / 26 (1)
TRA / 20-1 500 / 0.9979 / 20 / 100 (4) / 106 (2) / 100 (3) / 99 (5) / 100 (4) / 106 (2) / 100 (3) / 99 (5) / 100 (4) / 106 (2) / 100 (3) / 99 (5) / 107 (2) / 116 (9)
VEN / 5-1 000 / 0.9998 / 5 / 97 (5) / 101 (2) / 101 (1) / 93 (6) / 97 (5) / 101 (2) / 101 (1) / 93 (6) / 97 (5) / 101 (2) / 101 (1) / 93 (6) / 108 (1) / 116 (2)


Table SI2. Linearity, quantification limit (LLOQ), accuracy, precision and extraction recovery results for the developed C18 LC-MS/MS method. BIS: bisoprolol; CAR: carbamazepine; FLU: fluoxetine; LOS: losartan; LOS MTB: losartan metabolite; TEL: telmisartan; VAL: valsartan; VEN: venlafaxine. SD = standard deviation; RSD = relative standard deviation; QC = quality control; SW = surface water; WW = wastewater.

Pharma-
ceutical / Range (ng/L) / r² / LLOQ
(ng/L) / Within-run accuracy
(% (SD)) / Between-run accuracy
(% (SD)) / Within-run precision
(% RSD) / Between-run precision
(% RSD) / Extraction recovery
(% (SD))
QC
low
(n = 6) / QC
medium
(n = 6) / QC
high
(n = 6) / QC
low
(n = 18) / QC
medium
(n = 18) / QC
high
(n = 18) / QC
low
(n = 6) / QC
medium
(n = 6) / QC
high
(n = 6) / QC
low
(n = 18) / QC
medium
(n = 18) / QC
high
(n = 18) / SW
(n = 6) / WW
(n = 6)
CAR / 25-1 500 / 0.9998 / 25 / 102 (2) / 103 (2) / 102 (1) / 101 (3) / 104 (2) / 102 (1) / 2 / 2 / 1 / 3 / 2 / 1 / 110 (3) / 101 (6)
FLU / 1-60 / 0.9938 / 1 / 95 (4) / 101 (5) / 98 (4) / 94 (7) / 97 (6) / 98 (5) / 4 / 5 / 4 / 8 / 6 / 5 / 91 (2) / 87 (2)
LOS / 5-500 / 0.9992 / 5 / 92 (6) / 111 (6) / 111 (4) / 95 (9) / 106 (7) / 106 (8) / 7 / 5 / 3 / 9 / 6 / 8 / 92 (6) / 96 (5)
LOS MTB / 1-360 / 0.9967 / 1 / 101 (7) / 94 (9) / 98 (5) / 94 (14) / 94 (8) / 102 (8) / 7 / 10 / 5 / 13 / 8 / 6 / 96 (7) / 96 (7)
TEL / 1-360 / 0.9990 / 1 / 94 (9) / 89 (4) / 97 (5) / 93 (7) / 94 (10) / 97 (10) / 9 / 4 / 6 / 7 / 10 / 10 / 85 (1) / 91 (5)
VAL / 25-1 500 / 0.9987 / 25 / 94 (9) / 100 (4) / 104 (5) / 96 (7) / 99 (3) / 104 (5) / 9 / 4 / 4 / 7 / 3 / 5 / 98 (3) / 98 (4)
VEN / 5-1 000 / 0.9992 / 5 / 99 (2) / 100 (3) / 108 (1) / 103 (6) / 102 (3) / 103 (9) / 2 / 3 / 1 / 6 / 3 / 1 / 108 (1) / 100 (1)

Table SI3. Measured concentrations (in ng/L) of the pharmaceuticals in the sewage samples from the five catchment areas. STP= sewage treatment plant.

STP 1 / STP 2 / STP 3 / STP 4 / STP 5
Atenolol / 297 / 43 / 153 / 208 / 160
Bisoprolol / 19 / 3 / 6 / 16 / 4
Citalopram / 57 / 35 / 151 / 75 / 41
Fluoxetine / 10 / 8 / 26 / 8 / 11
Losartan / 36 / 29 / 36 / 36 / 45
Losartan carboxylic acid / 74 / 54 / 181 / 182 / 121
Telmisartan / 19 / 54 / 70 / 17 / 69
Valsartan / 150 / 162 / 200 / 183 / 372
Venlafaxine / 214 / 121 / 406 / 387 / 276
Carbamazepine / 647 / 316 / 786 / 402 / 593
Metformin / 37764 / 66232 / 21043 / 27462 / 20331
Tramadol / 380 / 370 / 636 / 326 / 439