The advent of a new pseudoephedrine product to combat methamphetamine abuse

Figures & data

Table 1. Three common methods for converting pseudoephedrine to meth.

1.	The “Birch method” is a chemical reduction reaction to convert pseudoephedrine in base form into methamphetamine. Although the method was developed by Authur John Birch in 1944, the method has become more popularly known as the Nazi method. Contrary to popular belief that the method was used extensively by the Nazis during World War II, the name is more likely to have come from an early methamphetamine cook having Nazi symbols on the recipe letterhead (16). The method is prevalent throughout the Midwest because of the ease of access to a raw material often used by farmers as fertilizer. The method is capable of producing multiple grams to kilogram quantities of methamphetamine, provided a methamphetamine maker has access to a sufficient supply of pseudoephedrine which can be obtained through mass buying of cold/allergy products containing pseudoephedrine HCl.
2.	The “Red Phosphorous method” is a chemical reduction reaction utilizing red phosphorus/hydriodic acid chemistry to convert pseudoephedrine to methamphetamine. The method is less prevalent in USA because of the need for specialized processing equipment and certain regulated chemicals. However, the Red Phosphorous method is the primary method used by Mexican “super laboratories” to make multiple kilogram/ton quantities of highly potent methamphetamine. On the street, this methamphetamine is known as “Mexican ice”.
3.	The “one-pot method”, also known as “shake-and-bake”, is a simplified variation of a Birch reduction method used to convert pseudoephedrine HCl tablets into methamphetamine. The method uses readily obtainable reactants and pseudoephedrine cold/allergy products to produce small quantities of low quality methamphetamine. All the ingredients are added to small, sealable vessels, such as 2-L soda bottles, and multiple simultaneous chemical reactions convert the pseudoephedrine HCl in the drug tablets into methamphetamine using little expertise or training.

Table 2. Percentage of pseudoephedrine HCl extracted from various solvents.

	Deionized water	Methanol	0.1 N HCL
Impede® 30 mg tablets	NR	NR	NR
Sudafed® 30 mg tablets	97	89	NT

NR = none recovered, a thick gel formed with Impede tablets when volumes up to 7.5 mL/tablet were added. Pseudoephedrine from these gels was not extractable. Higher volumes of solvent were not tested. NT = not tested.

Table 3. Methamphetamine recovery of control (Sudafed®) tablets and Impede tablets using various one-pot solvents.

	Solvent	Solids isolated (mg)	Total PSE HCl^a (mg)	Total meth HCl^a (mg)	Methamphetamine yield (%)^b
Methamphetamine recovery of control (Sudafed®) tablets using various one-pot solvents
Control RX1	Coleman fuel	2910	82	1813	67
Control RX2	Coleman fuel	2768	55	2104	78
Control RX3	7:3 heptane:ether	3527^c	176	1446	53
Control RX4	Hexanes	2445	49	1883	69
Mean	–	–	–	1811	67
RSD	–	–	–	15.1%	–
Methamphetamine recovery of Impede tablets using various one-pot solvents
Impede RX1	Coleman fuel	1121	157	773	29
Impede RX2	Coleman fuel	1949	0	1325	49
Impede RX3	7:3 heptane:ether	1593	239	988	37
Impede RX4	Hexanes	1612	65	984	36
Mean	–	–	–	1017	38
RSD	–	–	–	22.4%	–

^aThe weight of either methamphetamine HCl or PSE HCl contained in the solids isolated based on GC analysis of the isolate. ^bThe theoretical methamphetamine HCl yield from 3 g PSE HCl = 2.709 g. All of the % yield values are based on this number rather than 3 g PSE starting material. ^cThe high amount of isolated solids in the control 7:3 heptane:ether reaction is unexplained as the Impede® 7:3 heptane:ether reaction ran normally. It is expected that if the control 7:3 heptane:ether reaction was repeated that the amount of isolated solids would return to trend with the other control reactions.

Figure 1. Mean Pseudoephedrine Concentration-Time Profiles after Administration of Nexafed® Tablets and Control Tablets.

Table 4. Pharmacokinetic parameters of pseudoephedrine.

	Test product (Nexafed)			Reference product (Sudafed)
Parameter	n	Mean (SD)	CV%	n	Mean (SD)	CV%
Tmax (h)	30	2.10 (0.85)	40.59	30	1.93 (0.75)	38.91
Cmax (ng/mL)	30	206 (51.6)	24.97	30	223 (53.9)	24.15
AUClast (h ng/mL)	30	1852 (426.2)	23.01	30	1931 (450.3)	23.32
AUCinf (h ng/mL)	30	1963 (476.9)	24.29	30	2040 (496.1)	24.32
AUCExtrap (%)	30	5.36 (3.48)	64.94	30	5.05 (3.43)	67.91
λz (h^−1)	30	0.1337 (0.0259)	19.38	30	0.1375 (0.0267)	19.43
T1/2 (h)	30	5.40 (1.19)	21.97	30	5.25 (1.19)	22.60
Tlast (h)	30	24.01 (0.01)	0.05	30	24.00 (0.00)	0.02
Clast (ng/mL)	30	12.9 (7.27)	56.13	30	13.1 (7.22)	55.33

Full precision data used in pharmacokinetic analysis.

Table 5. Statistical analysis of the log-transformed systemic exposure parameters of pseudoephedrine.

Dependent	Geometric mean^a		Ratio (%)^b	90% CI^c		Power	ANOVA
variable	Test	Ref	(Test/ref)	Lower	Upper		CV%
ln(Cmax)	200.0541	216.5413	92.39	89.56	95.30	1.0000	7.09
ln(AUClast)	1807.6140	1882.4256	96.03	93.31	98.82	1.0000	6.54
ln(AUCinf)	1911.3434	1983.8007	96.35	93.33	99.47	1.0000	7.26

^aGeometric mean for the “test formulation (test)” and “reference product (ref)” based on least squares mean of log‐transformed parameter values.

^bRatio(%) = geometric mean (test)/geometric mean (ref).

^c90% confidence interval (CI).

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