Methods for impurity profiling of heroin and cocaine

46

Methods for impurity profiling of heroin and cocaine

Method D9:

Abundance of stable isotopes 

15

N and 

13

C by Isotope Ratio MS

(IRMS)

Sources: J. R. Ehleringer and others, “Tracing the geographical origin of cocaine”,

Nature, vol. 408, 2000, pp. 311-312; see also E. Ihle and H. L. Schmidt, “Multielement

isotope analysis on drugs of abuse: possibility for their origin assignment”, Isotopes

in Environmental and Health Studies, vol. 32, 1996, pp. 226-228.

Rationale for use: This IRMS method measures the relative abundance of the stable

isotopes 

15

N and 

13

C. The method is designed for unadulterated samples.

Outcome: Provides geo-specific information. Aids in the evaluation of samples for

case-to-case evidential purposes (linkage determinations [55]). Provides additional

information required to confirm links between samples, that is, the method should be

used in conjunction with a major component analysis.

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IV.

DATA HANDLING, INTERPRETATION

OF RESULTS AND APPROACH TO SETTING

UP PROFILING DATA COLLECTIONS

A critical factor for successful drug characterization and impurity profiling pro-

grammes is the availability of sufficiently comprehensive data collections for com-

parative purposes, within and between laboratories. While such data collections

can only be built gradually, the process must be continuous and ongoing. 

With regard to inter-laboratory comparison of data, the experience gained in

heroin analyses, both in the 1980s in the United States by DEA and, more recently,

by a group of European forensic laboratories in a harmonization study [48], has

shown that retrospective inter-laboratory database searches are not likely to be an

attainable goal in the immediate future. These experiences have shown that inter-

laboratory comparison of data generated using only major component analyses

can even be problematic. 

The most significant issue is quantitative reproducibility (variance) for sec-

ondary targets (i.e. not heroin or cocaine but other secondary alkaloids and impu-

rities). While this problem does not constitute an evidentiary issue, the variance

in the data is too large to allow for successful inter-laboratory database searches,

in other words, the average difference between samples of dissimilar origin his-

tory become ever smaller with increasing database size, because more groups of

samples from different origins start to overlap. In principle the incorporation of

trace impurity analysis data into a database search algorithm should greatly

enhance sample-to-sample comparison. Unfortunately, trace component analyses

generally have many more target analytes and typically the coefficients of vari-

ance in trace analysis are significantly greater than for major component analy-

sis. Hence, it is expected that the inclusion of trace component analysis data into

inter-laboratory database searches will significantly increase the complexity of the

comparison parameters without a comparable increase in comparison specificity.

It is because of these issues that nearly all retrospective database searches are per-

formed as an intra-laboratory operation. 

A.

Data handling

It is clear that the use of ratios of quantities, rather than absolute quantities, pro-

vides significantly better comparison data as this approach greatly reduces the

47

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48

Methods for impurity profiling of heroin and cocaine

magnitude of the analytical variance, in particular for the less abundant sample

components. For heroin and cocaine, one laboratory* has successfully applied

ratios for all major and minor components by expressing the ratios in terms of

the appropriate major analyte, morphine base or cocaine base. It is thought that

there is a significant advantage gained in employing this normalization calcula-

tion, as it allows the ready assessment of sample hydrolysis and, in some instances,

the positive comparison of two samples that are identical except for the extent of

hydrolysis. For cocaine, this entails summing the sample quantities of ecgonine,

ecgonine methyl ester, benzoylecgonine and cocaine, while for morphine it is cal-

culated from the sum of morphine, O3MAM, O6MAM and heroin. These calcu-

lations can be performed in several different manners where the exact method

employed for this calculation is much less important than is consistency in the

application. One example of such a calculation for morphine from a heroin sam-

ple is as follows:

Heroin hydrochloride sample

Quantitation results:

Heroin hydrochloride•H2O

= Hhcl

O6MAM hydrochloride•2-H2O

= O6hcl

O3MAM hydrochloride•2-H2O

= O3hcl

Morphine hydrochloride•3-H2O

= Mhcl

(303.45/375.85 * Mhcl) + (303.45/399.87 * (O3hcl +O6hcl)) +

(303.45/423.89 * Hhcl) = total morphine base content expressed as the

monohydrate.

While this calculation would be a tedious operation if performed by hand, it is a

trivial calculation for the computer. Using the data derived from major compo-

nent analyses, some laboratories have used in-house database search and classifi-

cation algorithms, in some cases with commercial neural network programs. The

success of those heroin and cocaine algorithms in determining sample origin is

due largely to the fact that both algorithms rely on the normalization of all com-

ponent ratios to morphine or cocaine content, respectively.

There are several other data handling approaches in current use by various

laboratories that also rely on the use of ratios in order to normalize the data.

Typically the ratios for cis- and trans-cinnamoylcocaine to cocaine and O6MAM

and acetylcodeine to heroin are determined. Some will also include ratios for tropa-

cocaine and/or norcocaine to cocaine, and papaverine and noscapine to heroin.

Then when two samples are found with very similar ratios, they are considered

to be possible “matches” and are selected for additional comparative analyses,

usually for trace components. 

The majority of those who perform these additional trace component analy-

ses for heroin use the procedure of Neumann and Gloger [56] or a modification

of that procedure. This procedure is a simple sulphuric acid extract whereby the

*Personal communication from Don Cooper, retired, Special Testing and Research Laboratory, Drug

Enforcement Administration, Dulles, Virginia, United States, 2005.

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