2007 Volume 12 Issue 1 Pages 73-82
The urinary concentrations of the main metabolites of methamphetamine (MA), specifically p-hydroxymethamphetamine-sulfate (p-OHMA-Sul) and p-hydroxymethamphetamine-glucuronide (p-OHMA-Gul) have been directly measured in MA users using an optimized LC-ESI MS method.
The concentrations of the main metabolites and unchanged MA in 50 MA users' urine ranged from 0.02 to 21.7 μg/ml for p-OHMA-Sul, from <0.02 to 2.43 μg/ml for p-OHMA-Glu, from <0.005 to 1.33 μg/ml for p-hydroxymethamphetamine (p-OHMA), from 0.01 to 6.79 μg/ml for amphetamine (AP) and from 0.04 to 133 μg/ml for MA, and the ratios of sulfate to glucuronide (S/G ratios) ranged from 2.2 to 37.1 (13.8±8.1). These results demonstrate that the majority of p-OHMA is eliminated as its conjugate and the sulfation is quantitatively more important than glucuronidation for the conjugation of p-OHMA in humans. The urinary concentration time-dependency in two MA users have also revealed that the conjugates were mostly excreted in urine within 3 days post-intake.
Both the acid and enzymatic hydrolysis conditions for p-OHMA conjugates were also optimized using the authentic standards of p-OHMA-Sul and p-OHMA-Gul. In the acid hydrolysis, the hydrolysis rate of p-OHMA-Sul was faster than p-OHMA-Glu, and a 3-h incubation with 1.2 mol/l HCl at 98 degrees Celsius gave complete hydrolysis of p-OHMA-Sul and p-OHMA-Glu. On the other hand, the enzymatic hydrolysis of two conjugates with Sulfatase Type H-1 from Helix pomatia required 6 hours for completion.
