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Letters to the Editor |
1 Division of General, Internal Medicine, Department of Medicine, 2
Division of Substance Abuse, Department of Psychiatry, and Behavioral Sciences, 3
Department of Epidemiology, and Population Health, 4
General Clinical Research Center, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York
5 Division of General, Internal Medicine, New York University, School of Medicine, New York, NY
aAddress correspondence to this author at: Internal Medicine Faculty Practice, Montefiore Medical Park, 1575 Blondell Ave. Bronx, NY 10461; Fax 718-405-8278, e-mail sberk{at}montefiore.org.
To the Editor:
Methadone maintenance is the primary treatment modality in the US for opioid dependence, with doses typically titrated to therapeutic response such as improvement of withdrawal symptoms or abstinence from drug use. Serum methadone concentrations are used to guide dosing in patients who do not respond to high methadone doses, may be poorly compliant, have excessive sedation or withdrawal symptoms, are pregnant, or have potential drug interactions.
In settings with limited onsite laboratory facilities, such as methadone maintenance clinics, it is common practice to collect blood samples in serum separator tubes (SST). The gel in the SSTTM forms a barrier between cells and serum after centrifuging, allowing for easier storage and transport. However, the gel in the SST may bind to and decrease the concentration of certain hydrophobic drugs, leading to erroneously low results (1)(2)(3)(4). Factors such as specimen volume, storage time, storage temperature, and the type of gel used by different manufacturers may influence the degree of binding (1)(2)(3)(4)(5). Because methadone is hydrophobic it is important to know whether methadone concentrations are affected by SST.
We collected serum samples from 8 participants in a study of the effect of pegylated interferon 
-2b on methadone pharmacokinetics. Each participant had 2 sets of blood samples drawn, 1 before and 1 after 2 weeks of pegylated interferon -2b administration. All participants were coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) and were receiving methadone in a methadone maintenance program.
Our Institutional Review Board approved the study, and informed consent was obtained from all participants on enrollment.
At both time points samples of 
5 to 8 mL were drawn directly and consecutively into 3 separate BD Vacutainer Tubes® (Becton, Dickinson and Company): 1) plain glass, 10 mL, no additive; 2) SSTTM glass, 9.5 mL; and 3) SST PLUS plastic, 8.5 mL. The tubes were allowed to clot for 15-min before centrifugation. Serum in the plain glass tube was withdrawn and immediately frozen at –100 °C, and serum in the glass or plastic SST was allowed to sit refrigerated at 4 °C for 4 h before being poured off and frozen at –100 °C. After thawing the frozen sera, methadone concentrations were determined by reversed-phase HPLC, as previously described (6).
In all 8 participants the mean (SD) methadone concentration decreased by 24.1 (10.5)% (range 9% to 46%), from 567 (286) µg/mL in plain glass tubes to 434 (224) µg/mL in glass SST (P <0.001; Fig. 1
). In 7 participants, serum was also collected in plastic SST, in which the mean methadone concentration decreased from 611 (278) µg/mL in plain glass tubes to 454 (207) µg/mL in plastic SST (P <0.001) (Fig. 1
). Compared with plain glass tubes, in these 7 participants, serum methadone concentrations decreased by 22.4 (9.3)% (range 9% to 41%) for samples collected in glass SST, and 25.6 (6.4)% (range 18% to 40%) for samples collected in plastic SST. The difference between glass SST and plastic SST was statistically significant (P = 0.04). There was no correlation between actual serum methadone concentration measured in plain glass tubes and percentage decrease in serum methadone concentration measured in either glass SST (r = –0.13; P = 0.6) or plastic SST (r = –0.08; P = 0.8).
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There was a greater mean percentage decrease in methadone concentration before compared with after pegylated interferon -2b administration in both glass SST [28.0 (12.4)% vs 20.1 (6.8)%] and plastic SST [28.0 (7.1)% vs 23.2 (5.2)%], but this effect was only statistically significant in glass SST (P = 0 .03).
The fact that serum from plain glass was frozen immediately, whereas serum from SST was refrigerated at 4 °C for 4 h before freezing (to simulate the clinical setting) is unlikely to explain this difference. It is unclear why the administration of pegylated interferon -2b seemed to partially ameliorate this effect. These data support the addition of methadone to the list of drugs whose concentration is known to be artificially decreased by collection in either plastic or glass BD Vacutainer SST. We conclude that plain glass non-SST tubes should be used to collect blood for serum methadone sampling.
Acknowledgments
This research was supported by the Center for AIDS Research of the Albert Einstein College of Medicine and Montefiore Medical Center (NIH P30-A1051519) and, in part, by a General Clinical Research Center grant (NIH M01-RR12248) awarded to the Albert Einstein College of Medicine of Yeshiva University.
References
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