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Faraz, Marzieh, Montaseri, Hashem, Bahaaldini Biggi Zarandi, Batool Faegheh. (1404). Development and Validation of an Enantioselective HPLC–UV Method for Stereospecific Therapeutic Drug Monitoring of Methadone Enantiomers in Iranian MMT Patients: A Pilot Study. سامانه مدیریت نشریات علمی, 12(1), 67-80. doi: 10.30476/tips.2026.110754.1352
Marzieh Faraz; Hashem Montaseri; Batool Faegheh Bahaaldini Biggi Zarandi. "Development and Validation of an Enantioselective HPLC–UV Method for Stereospecific Therapeutic Drug Monitoring of Methadone Enantiomers in Iranian MMT Patients: A Pilot Study". سامانه مدیریت نشریات علمی, 12, 1, 1404, 67-80. doi: 10.30476/tips.2026.110754.1352
Faraz, Marzieh, Montaseri, Hashem, Bahaaldini Biggi Zarandi, Batool Faegheh. (1404). 'Development and Validation of an Enantioselective HPLC–UV Method for Stereospecific Therapeutic Drug Monitoring of Methadone Enantiomers in Iranian MMT Patients: A Pilot Study', سامانه مدیریت نشریات علمی, 12(1), pp. 67-80. doi: 10.30476/tips.2026.110754.1352
Faraz, Marzieh, Montaseri, Hashem, Bahaaldini Biggi Zarandi, Batool Faegheh. Development and Validation of an Enantioselective HPLC–UV Method for Stereospecific Therapeutic Drug Monitoring of Methadone Enantiomers in Iranian MMT Patients: A Pilot Study. سامانه مدیریت نشریات علمی, 1404; 12(1): 67-80. doi: 10.30476/tips.2026.110754.1352

Development and Validation of an Enantioselective HPLC–UV Method for Stereospecific Therapeutic Drug Monitoring of Methadone Enantiomers in Iranian MMT Patients: A Pilot Study

Trends in Pharmaceutical Sciences and Technologies
مقاله 6، دوره 12، شماره 1، خرداد 2026، صفحه 67-80    اصل مقاله (646.17 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.30476/tips.2026.110754.1352
نویسندگان
Marzieh Faraz1؛ Hashem Montaseri* 1؛ Batool Faegheh Bahaaldini Biggi Zarandi2
1Department of Quality Control, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
2Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
چکیده
Methadone used in maintenance therapy is a racemic mixture of R- and S-enantiomers with distinct pharmacological and safety profiles. R-methadone mediates therapeutic effects via μ-opioid receptor activation, whereas S-methadone inhibits hERG potassium channels and may contribute to QT prolongation. Iran hosts the largest national methadone maintenance therapy (MMT) population (>800,000 patients), yet enantioselective therapeutic drug monitoring (TDM) is not available. To develop, validate, and clinically apply a simple and cost-effective HPLC–UV method for enantioselective quantification of methadone in plasma of Iranian MMT patients. Plasma samples from 20 clinically stable MMT patients (60-120 mg/day) were analyzed. Enantiomers were separated on a Chiral-AGP column (100 × 4 mm, 5 µm) using isocratic acetonitrile:0.01 M phosphate buffer (15:85, pH 6.8) at 1.2 mL/min with UV detection at 210 nm. Validation followed ICH Q2(R1) guidelines. Liquid–liquid extraction with n-hexane and imipramine as internal standard was applied. Calibration was linear (12.5-1000 ng/mL; r² ≥ 0.999). LOQ was 10 ng/mL. Intra- and inter-day precision were <3%, accuracy within ±3%, recovery 91–94%, and matrix effects 95–102% (CV <4.5%). Trough concentrations showed high variability: total methadone 452±185 ng/mL; R- 226±92 ng/mL; S- 181±74 ng/mL; R:S ratio 0.6-1.9. Only 45% of patients were within the therapeutic R-methadone range (100-250 ng/mL), while 10% exhibited potentially elevated S-methadone levels. This validated, low-cost (~$4/sample) method enables stereospecific methadone monitoring. Marked interindividual variability highlights the clinical value of enantioselective TDM to optimize efficacy and minimize cardiovascular risk in MMT programs.

تازه های تحقیق

Marzieh Faraz (Google Scholar)

Hashem Montaseri (Google Scholar)

کلیدواژه‌ها
Methadone Enantiomers؛ HPLC–UV؛ Therapeutic Drug Monitoring؛ Chiral Analysis؛ Methadone Maintenance Therapy؛ Stereoselective Pharmacokinetics
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