Page 35 - Advances in Forensic Applications of Mass Spectrometry - Jehuda Yinon

1522_C01.fm Page 22 Tuesday, December 2, 2003 10:05 AM

screening procedures for acidic drugs and/or metabolites. 67 If necessary,
quantification in plasma can be performed using GC/MS, 297–300 GC, 291,301–304
HPLC, 305–308 LC/MS-MS, 309,310 or modifications of these procedures. Enanti-
oselective determination has been reviewed by Tokuma and Noguchi. 311

1.4.1.2.4 Diuretics. Diuretics are misused mainly to reduce body weight.
The resulting hypokalemia may lead to severe cardiac disorders. Toxicological
screening for diuretics should be performed before extensive diagnostic work
is started. Diuretics are also misused for doping purposes and therefore, they
have been banned by the IOC. For both indications, screening is necessary. 1,312
Besides recent LC/MS procedures, 313–315 GC/MS procedures after (extractive)
methylation are preferred, 84,316–318 which simultaneously cover most of the
diuretics with series of other drugs relevant in clinical and forensic toxicology
or doping. 32,65–69,92,319

1.4.1.2.5 Antidiabetics of the Sulfonylurea Type. Antidiabetics of the
sulfonylurea type have been used since the 1950s in the treatment of hyper-
glycemia in diabetes mellitus. Besides this therapeutic use, sulfonylureas are
also misused. For differential diagnosis of unclear hypoglycemia, screening
is necessary to allow differentiation between a surreptitious misuse of sulfo-
nylureas or pathophysiological causes like insulinoma. Before exploratory
surgery or even subtotal pancreatectomy, misuse of sulfonylurea drugs should
analytically be excluded. Several LC or CE procedures have been published
for screening, confirmation, and/or quantification. 320–322 GC/MS after extrac-
32
tive methylation allowed only detection of the sulfonamide part, so that
differentiaton was not possible. LC/MS is much better for screening and
quantification of these drugs even in plasma. 25

1.4.1.2.6 Barbiturates. As already mentioned in Section 1.4.1.1.8, barbi-
turates have only weakly acidic properties; they can be detected in screening
and confirmation procedures for basic and neutral drugs 1,223 as well as acidic
drugs. 265 In order to improve the GC/MS sensitivity, derivatization by
9
ME, 90,259,265 ethylation, 260 or silylation is preferred. SPME was also applied. 72

1.4.1.2.7 Designer Drug of the Pyrrolidinophenone Type. As already
mentioned in Section 1.4.1.1.2, the new designer drugs alpha-pyrrolidi-
nophenone derivatives like PPP, MPPP, MPHP, MOPPP, and MDPPP are
mostly excreted as acidic metabolites. 178–181 Common screening procedures
did not cover such metabolites. Only mixed-mode SPE has proven to be
suitable for the extraction even of these zwitterionic metabolites and
181
showed good extraction yields. Common trimethylsilylation leads to best
GC/MS sensitivity.

© 2004 by CRC Press LLC