Methods for impurity profiling of heroin and cocaine

Methods for impurity profiling

31

Sample preparation: All glassware is silylated. Add 200 mg of the heroin sample to

4 ml of 1M sulphuric acid and 4 ml of a 3:2 mixture of diethyl ether and

dichloromethane, mix thoroughly. Centrifuge to separate phases and transfer 3 ml of

the organic phase into a clean reaction vial. Dry under dry nitrogen at 60° C.* Add

300 µl of the derivatization solution and 60 µl of the internal standard. Seal the reac-

tion vial tightly, mix thoroughly and heat at 70° C for 30 min. 

If method retention times shift more than 0.2 min, the instrument is recalibrated and/or

the retention time of the internal standard is adjusted by adjusting the carrier gas flow. 

Rationale for use: The method allows a total impurity profile of all alkaloidal trace

impurities. Several modifications of the above method are in use worldwide. This ver-

sion should provide the sensitivity and the specificity necessary for the analysis of

highly refined heroin samples, that is, highly refined hydrochloride samples from

South-East Asia. 

Outcome: Indication of general source region (South-East Asia, South-West Asia,

Mexico, South America). Sample comparisons for discrimination and evaluation of

samples for case-to-case evidential purposes (linkage determinations). Provides addi-

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

should be used in conjunction with a major component analysis.

*In this form, a tightly capped reaction vial can be stored for up to a week at -5° C prior to

further analysis.

4.

Residual solvent analysis

Method B5:

Dynamic headspace (thermal desorption) gas chromatography

(Conventional GC instrument)

Source:  J. Cartier, O. Guéniat and M. D. Cole, “Headspace analysis of solvents in

cocaine and heroin samples”, Science and Justice, vol. 37, No. 3 (1997), pp. 175-181.

Operating conditions: 

Detector:

FID, at 45 ml/min hydrogen and 450 ml/min air

Column:

DB-1 or equivalent , 60 m x 0.33 mm x 3.0 µm

Carrier gas:

Helium at 0.7 ml/min (column pressure 17 psig)

Injection 

technique:

1 µl; split, 30:1

Temperatures:

Injector: 280° C

Detector: 280° C

Oven: 35° C for 14 min, to 100° C at 5° C/min, to 245° C

at 7° C/min, no final hold (if petrol/gasoline was detected, the

temperature of the column was held at 245° C for 10 min)

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32

Methods for impurity profiling of heroin and cocaine

Internal standard: None

Sample preparation:* Weigh 250-300 mg of the powdered heroin sample into a 2-ml

GC derivatization vial. Add a 0.25-ml insert, containing approximately 100 mg of

activated carbon (charcoal strip). After sealing the vial, heat the contents for 60 min

at 80° C and allow to cool. Extract the activated carbon with 50 µl of carbon disul-

phide and inject 1 µl of this solution** into the GC.

Rationale for use: The method provides for the detection of 12 solvents in heroin sam-

ples, at detection limits between 2-15 parts per million (ppm) for 250-300 mg powder

samples. No special injector device is required; the method uses a conventional GC

instrument. Solvent analyses may be carried out on samples up to two years old.

Outcome: Provides additional information and an independent means of confirming

links from organic impurity and inorganic ion determinations.

Method B6:

Static headspace-GC/MS

(Special injector device required)

Source: Modified from D. R. Morello and R. P. Meyers, “Qualitative and quantita-

tive determination of residual solvents in illicit cocaine HCl and heroin HCl”, Journal

of Forensic Sciences, vol. 40, No. 6 (1995), pp. 957-963.

Operating conditions:

Detector:

Mass spectrometer, 70eV EI, 20-220 amu, 0.5 sec scan cycle

Column:

DB-1, 60 m x 25 mm x 1.0 µm

Carrier gas:

Helium, constant velocity approx. 30 cm/s

Injector 

technique:

Split 38:1, Tekmar 7000/7050 headspace autosampler

22 ml vials

Equilibration:

14 min at 85° C

2-ml loop; injection time: 0.3 min

Temperatures:

Loop: 175° C

Injector: 190° C

Injector transfer line: 175° C

MS transfer line: 190° C

Oven: 35° C to 150° C at 6° C/min to 180° C at 15° C/min,

hold for 10 min

*Preparation of headspace samples must be performed under clean laboratory conditions to

avoid solvent cross-contamination.

**The remainder of this sample can be reused for ICP-MS analysis.

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Methods for impurity profiling

33

Internal standard stock (ISS):* d

6

-acetone at 6 mg/ml, d

9

-2-chloro-2-methylpropane at

3.5 mg/ml,  d

14

-n-hexane at 1.5 mg/ml, d

8

-isopropanol at 7.5 mg/ml and d

8

-toluene at

1.5 mg/ml in dimethylsulfoxide (DMSO).** All standards should be +99.5% pure.

22% sodium sulfate solution: 220 gm of +99% anhydrous sodium sulfate in one litre

of deionized water. Between use, store at room temperature.

Dilute internal standard solution (DISS): Add 100 µl of the ISS for each 100 ml of

22% Na

2

SO

4

solution. Prepare daily.

Standard stock solutions (SSS): Methanol, ethanol, acetone, isopropanol, n-butanol and

isobutanol at 0.4 mg/ml; methyl ethyl ketone, ethyl acetate, chloroform, methylene

chloride, 1,1,2-dichloroethane, ethyl ether, methyl acetate, cyclopentane, isobutyl

acetate, n-butylethyl acetate and 1,1,1-trichloroethane at 0.2 mg/ml; cyclohexane, ben-

zene, toluene, n-hexane,  o-xylene,  p-xylene, mesitylene and mesityl oxide at 0.08

mg/ml. Two additional calibrations solutions are created by making two 1:5 serial

dilutions.*** All dilutions are made using a solution of DMSO:water (5:1). Label the

solutions SSSH, SSSM, SSSL respectively from the highest to the lowest concentra-

tion solution.

Calibration solutions: Add 5 ml of DISS to four 22-ml headspace vials, then add 50

µl of SSSH to the first vial, 50 µl of SSSM to the second vial and 50 µl of SSSL to

the third vial. The fourth vial is used as a run blank (standard zero point) as it con-

tains only the DISS. Immediately seal each vial tightly with a silicon/polytetrafluo-

roethylene (PTFE)-lined cap.

Sample preparation: Accurately weigh approximately 50 mg equivalent of heroin base

into a 22-ml headspace vial, add 5 ml of DISS. Immediately seal each vial tightly

with a silicon/PTFE-lined cap.

Rationale for use: The method provides facile detection to the 0.00001% level and

reproducible quantification to the low 0.0001% level relative to the heroin content

and, with minor modification, is utilized for both heroin and cocaine samples. The

method requires a special injector device. Also requires the acquisition of appropri-

ately deuterated standard materials; however, a few millilitres of the standard materi-

als will last for a considerable period of time. 

Outcome: Allows access to solvents trapped within the crystal matrices of samples

without decomposition of solvents or other sample components. The method provides

nearly comprehensive detection of all sample solvents and, very importantly, allows

the accurate assessment of the relative importance of the detected solvents.

*The internal standard stock is stable for up to two months if stored in the dark at -10° C

between uses.

**Deuterated standards were from the Cambridge Isotope Laboratories, 50 Frontage Rd.,

Andover, Massachusetts, United States.

***The calibration standards solutions were found to be stable up to four weeks if maintained

in the dark, at -10° C, between uses.

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