Methods for impurity profiling of heroin and cocaine

26

Methods for impurity profiling of heroin and cocaine

(morphine equivalent) of a highly refined South-East Asian heroin HCl. The neu-

trals extract from such a sample may contain a total of only 30-40 µgm of alka-

loidal-related neutral compounds with the triacetylnormorphine content accounting

for 10+% of the total. At these levels, a significant portion of the triacetylnor-

morphine is most likely to undergo hydrolysis during the analytical process.

Therefore, when comparing data obtained from neutrals extracts containing less

than 100 µgm total content, it is recommended that the response for those neu-

tral compounds having a clear degradation pathway available to them be summed

with their corresponding degradation products (i.e. add the response obtained for

triacetylnormorphine to the response obtained for N,6-diacetylnormorphine).

Additionally, the well-known potential for sample degradation within the injec-

tion port of the GC is definitely worth extra consideration. The strong polar char-

acter of the amidic alkaloidal-derived neutrals enhances the probability of

interactions with hot glass injection port liners. It is especially important for the

analysis of highly refined samples to use deactivated fused silica injection port

liners along with the addition of a relatively large excess of derivatization reagent

(such as MSTFA) to the sample, as these measures greatly reduce unwanted inter-

actions. Additionally, care should be exercised when carrying out the liquid-

liquid extraction in order to avoid degradation of the more susceptible compounds.

The dissolution of the sample in organic phase before the addition of the acid is

one very useful precaution. Typically, crudely refined sample extracts can be

stored as a dried residue in deactivated glassware for up to 24 hours without

detectable degradation of the sample. However, extracts obtained from highly

refined samples should be analysed immediately upon preparation. 

For certain sample types, the analytical data obtained from a neutrals extract,

when compared with the analytical data obtained from the major components,

affords a much higher comparison specificity. This is due to three significant

considerations:

(a)

Frequently there are many more valid comparison data points available;

(b)

Typically the bulk of the data points provide specific sample history

(such as processing information);

(c)

Typically larger arrays of opium alkaloids are represented in the neu-

trals fraction than are observed in the major component fraction. A few

of the important compounds that are represented in the neutrals frac-

tion, but absent in the major component fraction, are norlaudanosine,

thebaine, oripavine and the papaverubines. 

However, a neutrals extract of an uncut highly refined heroin sample may

provide less than six useable data points and, as a result, comparison specificity

for linkage purposes is often rather poor for those sample types. 

For those interested in the underlying chemistry of the neutral fraction com-

pounds, see Polonovski and Polonovski [41, 42] on the acetylation of N-oxides

and the articles by Mariella and Brown and related articles [44-46] on secondary

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Methods for impurity profiling

27

products obtained from the action of acetic anhydride on ring-bound tertiary

amines [37, 40-47]. Additionally, such compounds as N-acetylnorlaudanosine and

the  N-acetylated papaverubine isomers arise as simple acetylation addition prod-

ucts of alkaloids that are naturally present in opium as secondary amines.

Method B1:

GC method, without derivatization

Source: L. Strömberg and others, “Heroin impurity profiling: a harmonization study

for retrospective comparisons”, Forensic Science International, vol. 114, No. 2 (2000),

pp. 67-88.

Operating conditions:

Detector:

FID at 30 ml/min hydrogen, air at 400 ml/min

Column:

HP Ultra-2 or equivalent, 25 m x 0.20 mm x 0.11 µm

Carrier gas:

Helium at about 0.6 ml/min

Injection 

technique:

1 µl; split, 25:1

Make-up gas:

Helium at 30 ml/min.

Temperatures:

Injector: 300° C

Detector: 330° C

Oven: 160° C to 320° C at 6° C/min, hold for 6 min

Internal standard: Tetracontane at 10 mg/l in toluene

Sample preparation: Place an amount of sample equivalent to 15 mg of pure heroin

(equivalent to base) into a glass tube. Add 5.0 ml of 0.5N sulphuric acid to dissolve

the sample; then add 5.0 ml of internal standard solution. Mix thoroughly and then

centrifuge to separate the phases. Remove 3.2 ml of the internal standard solution and

evaporate to dryness. Add 200 µl of toluene and sonicate.

Reference chromatogram: See annex III, figure IV and table 3. The 16 selected ref-

erence peaks marked in the figure and presented in annex III, table 3, are used for

retrospective comparisons with a computerized data retrieval system. The experience

gained during a study of the national forensic science laboratories of Germany, the

Netherlands and Sweden is reported in reference [48].

Rationale for use: No derivatization,* relatively simple sample preparation and good

separations for nearly all components. Will not detect sugars and sensitivity probably

not sufficient for highly refined heroin samples. 

Outcome: Sample comparisons for discrimination and evaluation of samples for case-

to-case evidential purposes (linkage determinations). Provides additional information

required to confirm links between samples, that is, the method should be used in con-

junction with a major component analysis.

*See the subsection entitled “Hydrolysis of heroin” for possible problems related to the use

of methods that do not employ derivatization.

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