title: Quantitation of methadone and metabolite in patients under maintenance treatment.
abstract: Gas chromatography-mass spectrometry quantitative method was developed to monitor concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in plasma and urine of patients. The developed method was simple, accurate and reproducible to quantify methadone and EDDP in plasma and urine samples in the concentration range of 15-1,000 and 50-2,000 ng/mL, respectively. The proposed analytical method was applied to plasma and urine samples obtained from 96 patients undergoing methadone maintenance treatment (MMT) with daily methadone doses of 2-120 mg/day. Urinary methadone excretion was observed to be significantly affected by pH, in which the ratio of methadone to EDDP was two times higher in acidic urine (P = 0.029). The findings of this study further enhance the guidelines for monitoring of methadone treatment among outpatients. Methadone-to-EDDP ratio in urine was found to be consistent at 24 and 4 h, hence suggesting the possibility that outpatients may be monitored with single urine sample in order to check for compliance. This study which provides data on peak concentrations of methadone and EDDP as well as the ratio of both compounds has added to the body of knowledge regarding pharmacokinetic properties of methadone among heroin-dependent patients under MMT.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia shiauhui99@hotmail.com.
authors.forename: Shiau Hui
authors.initials: SH
authors.lastname: Diong
authors.affiliation: Drug and Research Unit, Department of Pathology, Hospital Kuala Lumpur, Jalan Pahang, 50586 Kuala Lumpur, Malaysia.
authors.forename: Nor Shuhadah
authors.initials: NS
authors.lastname: Mohd Yusoff
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Maw Shin
authors.initials: MS
authors.lastname: Sim
authors.affiliation: Drug and Research Unit, Department of Pathology, Hospital Kuala Lumpur, Jalan Pahang, 50586 Kuala Lumpur, Malaysia.
authors.forename: Raja Elina
authors.initials: RE
authors.lastname: Raja Aziddin
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Zamri
authors.initials: Z
authors.lastname: Chik
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Poppy
authors.initials: P
authors.lastname: Rajan
authors.affiliation: Department of Psychological Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Rusdi
authors.initials: R
authors.lastname: Abdul Rashid
authors.affiliation: Department of Psychiatry and Mental Health, Hospital Kuala Lumpur, Jalan Pahang, 50586 Kuala Lumpur, Malaysia.
authors.forename: Norliza
authors.initials: N
authors.lastname: Chemi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
mesh_terms: D000328:Adult; D000368:Aged; D002138:Calibration; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D003932:Heroin; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057230:Limit of Detection; D008297:Male; D008691:Methadone / Q000097:blood* / Q000652:urine*; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D010349:Patient Compliance; D011759:Pyrrolidines / Q000097:blood / Q000652:urine; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods; D015813:Substance Abuse Detection / Q000379:methods; D019966:Substance-Related Disorders / Q000097:blood / Q000188:drug therapy / Q000652:urine
chemical_list: D011759:Pyrrolidines; D003932:Heroin; D008691:Methadone; C010724:2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine