SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

A13
SCREENING FOR ACE INHIBITORS AND AT-II-ANTAGONISTS IN URINE BY LC-MSIMS
Barbora MaraIikova 1 ,2, Wolfgang Weinmann 1 , Claudia A. Muellerl,'
lInstitute of Forensic Medicine, University Hospital, Albertstr. 9, D 79104 Freiburg (Germany)
Phone: ++49 7612036878, Fax: ++49 761 2036858, Email: muel1erc@ukl.uni-freiburg.de
2University of Par dub ice, FCHT, Department of Analytical Chemistry, nam. Cs.legii 565, 53210
Pardubice, Czech Republic
For the detection of Angiotensin-Converting Enzyme inhibitors (ACE inhibitors: enalapril, Iisinopril,
perindopril, captopril, ramipril, cilazapril as prodrug and active drug) and Angiotensin-II-Receptor
Antagonists (candesartan, eprosartan, irbesartan, \osartan, telmisartan, valsartan) an LC-MS/MS target
screening method has been developed to be used in clinical and forensic toxicological analysis. These drugs
are widely used for lowering blood pressure besides betablockers, diuretics and calcium channel blockers ­
which have been the aim of our previous work [I] - and their intake after prescription or even the non­
compliance of patients, not taking the drugs, could have severe effects on traffic safety. Furthermore,
overdosage ofthese drugs can cause severe lowering of the blood pressure.
For method development by LC-MSIMS ESI and APCI mass spectra of the compounds have been
compared. ESI was found to be more suitable in terms of sensitivity for the ACE inhibitors, whereas the
AT -II-Receptor Antagonists were detectable by both ionization modes.
Linearity for quantitation was found for captopril, cilazapril, enalapril, Iisinopril, perindopril, ramipril and
ramiprilat in the range of 10 to 500 nglmL with ESI after extraction from urine. LOD was below 10 ng/ml
in urine. In patients' urine samples the ACE inhibitors were detectable in their active form (carboxylic
form) by electrospray ionization after intake of therapeutic doses. However, the active form was not
available as reference substance for all compounds and had to be generated by hydrolysis of the esters. The
internal standard still remains a problem for quantitative analysis, since deuterated compounds are not
available. For patients' urine and serum samples Benazepril was used as internal standard for quantitation,
since it was not prescribed for these patients.
Method development for the sartanes included liquid-liquid extraction (LLE). LC-ESI-MRM was found to
be suitable for target screening for these drugs after spiking to urine; irbesartan was detected in a forensic
case.
Results of the method development and applications to patients' urine and also some serum samples are
presented.
[1] Mueller CA, Baranda AB, Weinmann W. Screening for l,4-dihydropyridine calcium channel blockers
in plasma and serum by solid-phase extraction and LC-MS-MS. J Mass Spectrom (in Press, 2004).
Keywords: ACE inhibitors, AT II antagonists, LC-MS/MS
Page 127