Nguyen Nguyen (Presenter)
Soloniuk Pain Center
Bio: Nguyen Nguyen is a technical director at the Soloniuk Pain Center and the Redding Opioid Recovery Medical Clinic in Redding, CA. The laboratory services urine drug testing for pain management and addiction therapy.
Authorship: Nguyen Nguyen PhD, Paul Scipione MD, Theodore Workman MD, and Leonard Soloniuk MD
Soloniuk Pain Center and Redding Opioid Recovery Medical Clinic
| Short Abstract When scheduled substances are prescribed, Urine Drug Test (UDT) results are necessary for clinical decisions. While UDT can detect recent methamphetamine use, it could not distinguish between illegal S-methamphetamine and legal R-methamphetamine use. At Soloniuk Pain Center (SPC) and Redding Opioid Recovery Medical Clinic (RORMC) in Northern California, review of enantiomeric confirmation was conducted to determine if chiral testing is necessary in these two unrelated patient populations. Of the 100 methamphetamine positive samples, S-methamphetamine was found in 70% of the SPC samples and 100% of the RORMC samples. With a 30% R-methamphetamine confirmation rate, chiral analysis for chronic pain patients is essential for informed clinical decision-making. |
Long Abstract
Background
Methamphetamine is one of the top drugs of abuse in Northern CA and is linked to increased hospitalizations and mortality.1,2 Methamphetamine is routinely tested in UDT (Fig. 1). The illegal S-methamphetamine, which produces an instant euphoric rush in most users, is three to four times more potent to the CNS than R-methamphetamine, resulting in a different phamaco-physio-psychologic effect.3 The less potent R-methamphetamine, which is found in over-the-counter medications, can be obtained legally from various sources.4 Clinician confidence in UDT results is imperative, as UDT results for drug compliance in both the chronic pain and opioid abuse patient populations impact patient care.
This study analyzed 100 methamphetamine enantiomeric results from two different subsets of patients in Northern California: patients undergoing pain management at SPC; and patients undergoing addiction treatment at RORMC. A chromatographic separation method using Chirobiotic V column, which contains gel made up of Vancomycin with 18 chiral centers forming cavities that are capable of differentiating the enantiomorphs, was validated to discriminate S and R isomers.
Methods
-Sample Preparation
Confirmatory testing was carried out by b-glucuronidase hydrolysis and liquid-liquid extraction methods validated in-house. Positive methamphetamine samples from confirmatory UDT were submitted for enantiomeric identification via chiral chromatographic separation: 63 samples from SPC from 6/2014 to 11/2015, and 37 samples from RORMC from 7/2015 to 11/2015. S and R-methamphetamine suitability standards were prepared at 667 ng/mL. Dilution of methamphetamine samples with concentration over 2500 ng/mL was done using the mobile phase to prevent column overload and/or detector saturation.
-Methods and Evaluation
Waters Acquity tandem Xevo TQD was used for enantiomer testing. Enantiomers were separated by isocratic flow using 0.01% ammonium hydroxide, 0.1% acetic acid in methanol on Astec Chirobiotic V (5um, 250x4.6mm) at flow rate 1mL/min at ambient temperature. The TQD monitors two ES+ transitions m/z 150.03>119.05, and m/z 150.03>91.03 over 21 minutes. Identification of enantiomers was accomplished by comparing retention times (RT) of samples to RT of S-methamphetamine (14.00min) and R-methamphetamine (14.95min) standards (Fig. 2).
Results
Methamphetamine Samples Size
SPC n=63
RORC n=37
Methamphetamine Positive per Week
SPC 0.81
RORC 1.64
Methamphetamine Positive per Total Volume
SPC 0.01
RORC 0.24
R-Methamphetamine Confirmation Rate
SPC 30%
RORC 0%
S-Methamphetamine Confirmation Rate
SPC 70%
RORC 100%
Discussion
The two distinct patient populations– one comprised of pain care patients, the other opioid recovery patients– resulted in different study outcomes. Methamphetamine positives were 0.01% and 0.24% of total samples from SPC and RORMC respectively (Table 1). From the retro-analysis of all methamphetamine positives found within the timeframe of this study, S-methamphetamine was confirmed in 70% of samples from SPC and 100% from RORMC (Fig. 3). On average, SPC had 0.81 methamphetamine positives per week, while RORMC had 1.64 methamphetamine positives per week. Chronic pain patients use methamphetamine less frequently and have a lower detection rate of S-enantiomer than opioid abuse patients.
From the patient demographic comparison, methamphetamine discrimination protects pain patients from false accusation of breach of the controlled substance agreement. In these patients, routine UDT is not a complete indicator of drug compliance and may misconstrue the reliable clinical picture, negatively impacting the physician-patient relationship and treatment plans for the patient. However, for patients undergoing addiction treatment at RORMC, enantiomeric testing is at the discretion of the provider.
Conclusion
Routine confirmation of methamphetamine positives by enantiomeric identification is necessary for chronic pain patients undergoing controlled substance management. These patients may have legitimate reasons for using legal products, which only contain R-methamphetamine. In contrast, S-methamphetamine positive results are expected in opioid abuse patients, as this demographic historically, or by admission, use illicit drugs.
Enantiomeric confirmation in certain populations and circumstances is a necessary effort for accurate and safe clinical decision-making. In chronic pain patients, routine enantiomeric testing for methamphetamine increases clinician confidence and healthcare quality for patients with positive methamphetamine results.
References & Acknowledgements:
1. Nguyen N, Workman T, Soloniuk L. (2015). The Positive Inconsistent in Urine Drug Testing at a Community Specialty Pain Clinic. Poster session presented at: The Association for Mass Spectrometry Applications to the Clinical Lab. 7th Annual Conference; March 28- April 1; San Diego, CA.
2. Callaghan RC, Cunningham JK, Verdichevski M, Sykes J, Jaffer SR, Kish SJ. (2012). All-cause mortality among individuals with disorders related to the use of methamphetamine: a comparative cohort study. Drug and Alcohol Dependence, 125(3), 290-294.
3. McConathy J, Owens MJ. Stereochemistry in Drug Action. (2003). Primary Care Companion to the Journal of Clinical Psychiatry, 5(2): 70-73.
4. Mussoff F. (2000). Illegal or legitimate use? Precursor compounds to amphetamine and methamphetamine. Drug Metabolism Reviews. 32(1), 15-44.
Support for this study was funded by the SPC and the RORMC. We thank Pa Nhia Vang for Fig. 3, and Linda Soloniuk, RN, BSN, MA for editorial assistance.
| Description | Y/N | Source |
| Grants | no | |
| Salary | yes | Soloniuk Pain Center |
| Board Member | no | |
| Stock | no | |
| Expenses | no |
IP Royalty: no
| Planning to mention or discuss specific products or technology of the company(ies) listed above: | no |