Page 85 - Advances in Forensic Applications of Mass Spectrometry - Jehuda Yinon

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phine in blood indicated a short survival time after drug intake. In the next
39
study, Bogusz et al. extended the LC/APCI/MS method for the determina-
tion of 6-MAM, M3G, M6G, morphine, codeine, and C6G, using deuterated
internal standards for each compound. The detection limits ranged from 0.5
to 10 mg/l. This method was applied for routine forensic examination of
blood samples taken from suspected heroin abusers. 7
In the last few years, several LC/MS methods for determination of mor-
phine, codeine, and corresponding glucuronides were published. The meth-
ods were generally based on solid-phase extraction and ESI/MS or
ESI/MS/MS detection and are summarized in Table 2.1. Determination of
free morphine and both its glucuronides in body fluids may be helpful in
the interpretation of a given case from a forensic and clinical point of view.
High free-morphine fraction generally indicates acute poisoning in a very
early stage, particularly in a person who has not taken heroin or morphine
chronically. Also, the differentiation between pharmacologically active M6G
and inactive M3G, as well as the free morphine:morphine glucuronides ratio,
is of practical importance for interpretation of the severity of poisoning. 45
The Naidong group applied ultrafast LC/MS/MS of morphine and its glu-
24
curonides, using the combination of short (50 ¥ 3 mm), straight-phase
column and high flow rate (4 ml/min).
It must be stressed that heroin after deacetylation follows metabolic
routes which are common with morphine and — to some extent — also with
codeine. Therefore, only 6-MAM may be regarded as a heroin-specific metab-
olite and as a marker of heroin use, and is detectable in blood and urine
samples of heroin addicts. 7,38,45 Strictly speaking, the presence of 6-MAM in
urine, blood, or other body fluids evidences the intake of pure diacetylmor-
phine (DAM). The differentiation between the intake of pure DAM and illicit
heroin became relevant after the introduction heroin prescription programs
in some countries like Switzerland, Great Britain, Germany, and the Neth-
erlands. One of the basic requirements of these programs is that the partic-
ipants must not use any illicit drugs, particularly illicit heroin. In illicit heroin
not only DAM is present but also several other opiates like 6-MAM, acetyl-
codeine, codeine, papaverine and noscapine, as well as various adulterants.
It must be stressed that only acetylcodeine (AC) may be regarded as a specific
marker of illicit heroin. AC is produced from codeine during the acetylation
of opium. Its content in illicit heroin ranges from 2 to 7%. O’Neal and
46
Poklis 47,48 developed a GC/MS method for detection of AC in urine and found
this drug in over 30% of morphine-positive specimens in concentrations
ranged from 1 to 4600 mg/l. 6-MAM was found in over 70% of these samples.
Codeine — a possible metabolite of AC — was found in all urine samples.
Staub et al. used also GC/MS and detected AC in over 85% and 6-MAM
49
in over 94% of 71 urine samples obtained from illegal heroin consumers.

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