Laboratory Analysis of the Conversion of Pseudoephedrine
to Methamphetamine From Over-the-Counter Products

Robert P. Bianchi, BS*
Prescription Drug Research Center
Mason Enterprise Center
4031 University Drive, Suite 200
Fairfax, VA 22030
[email: RBconsulting700 -at- aol.com ]

Manoj N. Shah, PhD, David H. Rogers, PhD, and Thomas J. Mrazik, PharmD
Medical Information & Communications
McNeil Consumer & Specialty Pharmaceuticals
7050 Camp Hill Road
Fort Washington, Pennsylvania 19034

Presented in part at the American Pharmacists Association Annual Meeting, Orlando, Florida, April 1‑5, 2005.

ABSTRACT: Two approaches to convert pseudoephedrine (PSE) to methamphetamine from over-the-counter (OTC) PSE products were examined. The first approach was two-step, and involved PSE extraction followed by conversion using the Birch (Nazi) method. Multiple-active products containing PSE and 2 - 4 actives were tested, including caplet, tablet, liquid, and liquid-filled softgel forms. The extent of conversion to methamphetamine varied among the extracts, and was up to 30.7 percent of the PSE present in the starting product. PSE extract conversion to methamphetamine was realized regardless of dosage form (i.e., whether solids, liquids, or liquid-filled softgels were used). The second approach involved direct conversion of PSE to methamphetamine using the Birch method. Materials tested included pure PSE powder, and also a combination of PSE plus an analgesic as either a powder mixture or as an OTC caplet. The extent of conversion to methamphetamine ranged from 54.1 to 67.7 percent of the PSE present in the starting material. These results provide scientific proof that PSE from solid and liquid OTC products can be converted to methamphetamine using either extraction or direct approaches (both employed by small clandestine laboratory operators). The ease and extent of PSE conversion from extracts appears to be independent of the PSE starting quantity, dosage forms, and presence of other actives.

KEYWORDS: Acetaminophen, Birch Method, Dextromethorphan, Extraction, Guaifenesin, Methamphetamine, Nazi Method, OTC PSE Products, Pseudoephedrine, Forensic Chemistry

Introduction

Methamphetamine abuse has reached widespread proportions in the United States, causing serious social, economic, and environmental problems for communities, and draining scarce law enforcement resources (1-4). Currently, thousands of small toxic laboratories (STLs) are seized annually throughout the country, especially in the Midwest and western states. With very few exceptions, these laboratories are not operated by professional chemists, but rather by “cooks” who have learned from other “cooks”, the Internet (5), or from underground publications (6). Production scales are typically one ounce or less, and are intended for personal use and/or limited distribution. It is estimated that approximately 35 percent of the methamphetamine used in the United States comes from small-scale laboratories (7).

At present, the most popular precursor used for the clandestine manufacture of methamphetamine is pseudoephedrine (PSE) contained in over-the-counter (OTC) sinus and cold preparations (8). The preferred starting material has been single-ingredient tablets (i.e., containing no other active ingredients). The PSE in these products are extracted with alcohol, filtered, and converted to methamphetamine via the Birch reduction method (Nazi method) or one of the red phosphorus methods (9,10). The first step in this study was therefore to determine the efficiency of extracting PSE from a variety of dosage forms, with subsequent conversion to methamphetamine using the Birch reduction method, which is currently the most popular among STL “cooks.” The second approach was to directly convert PSE or PSE-containing OTC products to methamphetamine, without the preliminary extraction step, again using the Birch reduction method.

Experimental

The described experiments were conducted by National Medical Services, Willow Grove, Pennsylvania, an independent forensic laboratory accredited by the American Society of Crime Laboratory Directors - Laboratory Accreditation Board (ASCLD-LAB).

Pseudoephedrine Extraction Followed by Birch Method Conversion
A simple extraction process was performed on three multiple-active ingredient OTC products, each of which contained PSE, the pain reliever acetaminophen, and up to two other active ingredients (Table 1). The process involved grinding the tablets or caplets (modified for liquid-filled softgels), dissolving the resulting powder or liquid in denatured ethanol, filtering to isolate the solution, evaporating it to a small volume, adding acetone to precipitate the PSE, and collecting the precipitate by filtration. The procedure was conducted on a large scale (equivalent to 7.5 grams of PSE (i.e., 250 tablets/caplets or 100 liquid-filled softgels)) to simulate a typical small-scale illicit methamphetamine synthesis. The recovered PSE was directly submitted to the Birch reduction method. The method involves dissolution of the PSE in anhydrous ammonia, and then adding lithium metal (9). Quantitative analysis of the recovered PSE (and other active ingredients) from the first step, and of the methamphetamine and unreacted PSE from the second step, were performed using liquid chromatography/tandem mass spectrometry (LC/MS/MS).

Because illicit laboratories are known to employ additional extraction techniques (in addition to the method described above), five multiple-active OTC products, each of which contained PSE, acetaminophen, and up to 2 additional active ingredients (Table 1), were submitted to a more complex extraction process. This latter procedure involved dissolution of the sample in dilute hydrochloric acid, washing with a naphtha-based organic solvent to remove polymers, waxes, and other inert ingredients, alkalinization to form PSE base, two extractions with toluene to isolate the PSE base, and then conversion of the PSE base back to the HCl salt. The complex extraction was also conducted on a 7.5 gram PSE scale (250 caplets, 100 softgels, or 600 mL of liquid). quantitative analysis of the extracts and synthesized methamphetamine was again conducted by LC/MS/MS.

Direct Birch Method Conversion
Pure PSE powder, a mixture of PSE and acetaminophen powder, and ground caplets containing PSE and acetaminophen were directly subjected to the Birch reduction method, and the resulting products were subjected to quantitative analysis by LC/MS/MS. The quantity of PSE in each of the starting materials was 0.2 grams, 0.2 grams, and 0.18 grams, respectively.

Results and Discussion

Pseudoephedrine Extraction Followed by Birch Method Reduction
The results demonstrated PSE conversion to methamphetamine from all of the PSE precipitates subjected to the Birch method reduction (Table 2). The percentage of PSE in the starting OTC product that was converted to methamphetamine ranged from 0.3 to 30.7 percent. The conversion efficiency was comparable for PSE solid forms (ranging from 3.0 to 100 percent of the PSE in the extract being converted to methamphetamine) and PSE liquid forms (ranging from 37.5 to 100 percent of PSE in the extract being converted to methamphetamine). The starting quantity of PSE and the presence of other ingredients did not appear to affect the extent of conversion.

Direct Birch Method Conversion
Direct conversion of pure PSE powder was performed as a baseline reference. A second, powdered mixture of PSE (0.2 g) and acetaminophen (1.0 g) was used to assess the potential for interference from acetaminophen in the conversion process (since many of the OTC medications contain a high proportion of acetaminophen). A third experiment using an OTC tablet product containing PSE and acetaminophen was used to further verify the potential of direct conversion (6 tablets containing 0.18 g PSE and 3.0 g acetaminophen were ground using a mortar and pestle). The results confirmed PSE conversion to methamphetamine from all PSE forms, with 54.1 to 67.7 percent conversion of PSE to methamphetamine (Table 2). The results for PSE plus acetaminophen (i.e., powder and caplet) were comparable to those of PSE powder alone. Based on the results from the PSE extraction, it would be expected that direct conversion would also succeed for liquid and soft-gel forms.

Conclusions

The results of this study demonstrated that OTC sinus and cold preparations containing PSE can be converted to methamphetamine either directly or following a PSE extraction procedure, from both single- and multiple-active ingredient formulations. This study provides scientific proof that virtually any OTC product containing PSE can be used to manufacture methamphetamine (11,12). That is, the potential for methamphetamine production from PSE-containing OTC products is independent of dosage form (solid, liquid, or liquid-filled softgel), presence of actives, and formulation variations.

Acknowledgements

The authors thank Dr. Kevin Ballard, MD, PhD, and David Easterling, MS, National Medical Services, Willow Grove, Pennsylvania, for performing the extractions, methamphetamine synthesis, and chemical analyses for these experiments.

[Funding support: This study was funded by McNeil Consumer & Specialty Pharmaceuticals.]

References

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9. Schucker D. Nazi labs. AONE Journal At http://www.okienarc.org/nazilab.htm . Accessed July 22, 2005.

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11. Bremer N, Woolery RJ. The yield of methamphetamine, unreacted precursor and Birch by‑product with the lithium-ammonia reduction method as employed in clandestine laboratories. Newsletter of Midwestern Association of Forensic Scientists 1999; Fall:8-16.

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Table 1. Active Ingredients Per Dosage Unit Included in Tested OTC PSE Products.

Product Identifier	Dosage Form	Decongestant (mg)	Analgesic (mg)	Antihistamine (mg)	Antitussive (mg)	Expectorant (mg)
PSE Simple Extraction Followed by Birch Method Conversion
1	Caplet	PSE (30)	APAP (500)	-	-	-
2	Tablet	PSE (30)	APAP(325)	-	-	GUA(200)
3	Liquid Filled Softgel	PSE(30)	APAP(250)	-	DXM(10)	GUA (100)
PSE Complex Extraction Followed by Birch Method Conversion
1	Caplet	PSE(30)	APAP(500)	-	-	-
4	Caplet	PSE(30)	APAP(500)	CLR(2)	-	-
5	Caplet	PSE(30)	APAP(325)	-	DXM(15)	GUA (200)
3	Liquid Filled Softgel	PSE(30)	APAP(250)	-	DXM(10)	GUA (100)
6	Liquid	PSE(30)	APAP(500)	DOX(6.25)	DXM(15)	-

APAP - Acetaminophen; CLR - Chlorpheniramine; DOX - Doxylamine; DXM - Dextromethorphan; GUA - Guaifenesin; OTC - Over-the-Counter; PSE - Pseudoephedrine.

* * * * *

Table 2. Results of Methamphetamine Conversion of OTC PSE Products.

Product Identifier	Dosage Form	Quantity of PSE in Starting Product/ Material (grams)	Percent PSE in Extract from Product	Methamphetamine Conversion
				Percent PSE in Extract Converted to Methamphetamine	Percent PSE in Starting Products/ Material Converted to Methamphetamine
PSE Simple Extraction Followed by Birch Method Conversion
1	Caplet	7.5	11.0	3.0	0.3
2	Tablet	7.5	6.5	7.7	0.5
3	Liquid Filled Softgel	3.0	14.8	37.5	5.6
PSE Complex Extraction Followed by Birch Method Conversion
1	Caplet	7.5	30.7	100.0	30.7
4	Caplet	7.5	25.2	61.4	15.5
5	Caplet	7.5	41.1	51.4	21.1
3	Liquid Filled Softgel	3.0	5.5	84.6	4.7
6	Liquid	1.2	5.4	100.0	5.4
PSE Conversion by Direct Birch Method (No PSE Extraction Step)
PSE HCl Powder		0.2	-	-	67.7
PSE HCl + APAP Powder		0.2	-	-	65.5
PSE HCl + APAP Caplet		0.2	-	-	54.1
APAP - Acetaminophen; OTC - Over-the-Counter; PSE - Pseudoephedrine.