Opioids

Opioids are a class of drugs used therapeutically to treat pain, coughs and diarrhea. They are also abused because of the euphoric effects that they produce. The prototypical opioid is morphine. From morphine, the synthetic opioid diacetylmorphine or heroin is produced. Although heroin remains the most commonly abused opioid, there are other opioids that are abused. For instance, methadone is an opioid used to treat opioid addiction and is also used to treat chronic pain. Advantages to the therapeutic use of methadone include good oral bioavailability and a much longer half-life than morphine. Oxycodone is another synthetic opioid that is used to treat pain. Recently, a sustained release form of oxycodone was produced as a way of utilizing the efficacy of oxycodone, but with a longer duration of action. Because of the abuse of this sustained release form, the higher dose form was subsequently removed from the market by the manufacturer. Another synthetic opioid, fentanyl, is used in the operating room as an adjunct to anesthesia. Fentanyl is also available in transdermal patches that are prescribed to treat chronic pain. Fentanyl and its analogs have appeared as abused drugs in various parts of the country (23).

Because opioids are a common source of drug intoxication, the toxicology laboratory must be able to look for these compounds. The most common method to screen for opioids is immunoassay. The commercially available opioid immunoassays are designed to detect morphine and codeine. Most of these immunoassays do not have good detection limits for the other opioids discussed above. However, there are immunoassays that have been designed to specifically detect these compounds. As an example, Table 3 lists the cross-reactivities of oxycodone to opiate immunoassays and to specific oxycodone/oxymorphone immunoassays. The general opiate assays have cross-reactivities to oxycodone of <21%; as expected, the specific oxycodone immunoassays have greater cross-reactivities to the drug.

Table 3

Oxycodone Cross-Reactivity in Commercially Available Opiate Immunoassays1

Cutoff

Assay

Abuscreen® ONLINE Opiates CEDIA® Opiate Assay Emit® d.a.u.® Opiate Emit® II Plus Opiate Immunalysis Opiates Direct ELISA

Immunalysis Oxycodone Direct ELISA

Neogen® Opiate Group ELISA Neogen® Oxymorphone/Oxycodone ELISA OraSure Opiates

Cutoff

Oxycodone

concentrations)

Intended specimen

% reactivity

Calibrator

tested

types

<0.3%

Morphine

300 ng/mL

Urine

3.1%

Morphine

300 ng/mL

Urine

6.7%

Morphine

300 ng/mL

Urine

5.6%

Morphine

300 ng/mL

Urine

21%

Morphine

25 ng/mL

Whole blood, oral

fluids, serum, plasma,

urine

100%

Oxycodone

10 ng/mL

Whole blood, oral

fluids, serum, plasma,

urine

10%

Morphine

Not available

Multiple matrices

400%

Oxymorphone

Not available

Multiple matrices

2.0%

Morphine

Not available

Multiple matrices

a Data from manufacturer package inserts.

Abundan 1.0

e TIC

Methadone (9.50 min.)

0.8 2 0.6

Internal Standard (10.28 min.)

0.4

Oxycodone (11.25 min.)

0.2

1

K. . II jL,

Fentanyl (11.96 min.)

Time-

-> 8.00 9.00

10.00

11.00

12.00 13.00 14.00

Methadone

Abundan 1.0

0.4 0.2

_

Time--

> 9.10 9.30 9.50 9.70 9.90 Time--> 9.10 9.30 9.50 9.70 9.90 Time-

> 9.10 9.30 9.50 9.70 9.90

Internal Standard

Ion 86 10.28 min.

Ion 165 10.28 min.

Time-- > 9.90 10.10 10.30 10.50 10.70 Time-- > 9.90 10.10 10.30 10.50 10.70

Abunda

Oxycodone

Abundan 1.6

0.4

i_

11.25 min.

l 10

I

u

Ion 115 11.25 min.

Time--

> 10.90 11.10 11.30 11.50 11.70 Time-- > 10.90 11.10 11.30 11.50 11.70 Time-- > 10.90 11.10 11.30 11.50 11.70

Fentanyl

0.2

Ion 245

11.96 min.

I_

Ion 189 11.96 min.

Time--

00 > 11.60 11.80 12.00 12.20 12.40 Time-- > 11.60 11.80 12.00 12.20 12.40 Time-- > 11.60 11.80 12.00 12.20 12.40

Fig. 2. Chromatogram of the three opioids within a single chromatographic run.

There are a number of analytical methods available to detect a larger group of opioids. A laboratory can combine a general opioid immunoassay with specific immunoassays for methadone, oxycodone and fentanyl. Alternatively, a gas chromatographic method using a methylphenylsilicone or dimethylsilicone column can simultaneously detect methadone, oxycodone and fentanyl. No derivatization is required and either a nitrogen-phosphorus or a mass selective detection system can be used. Figure 2 is a chromatogram of the three opioids within a single chromatographic run. However, the opioid immunoassay must still be included, as morphine does not elute well from these columns without derivatization (23).

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