Convulsant Effects of Street Heroin -- Neurotransmitter.net

(Created 2/16/04)

O'Neal CL, Poklis A, Lichtman AH.
Acetylcodeine, an impurity of illicitly manufactured heroin, elicits convulsions, antinociception, and locomotor stimulation in mice.
Drug Alcohol Depend. 2001 Dec 1;65(1):37-43.
"Acetylcodeine is one of the major impurities present in illicitly manufactured heroin (diacetylmorphine). Data on its pharmacology and toxicology are limited and its ability to alter the toxic effects of diacetylmorphine is not known. The first objective of the present study was to compare the acute pharmacological and toxicological effects of acetylcodeine to those of codeine and diacetylmorphine in mice by assessing nociception in the tail-flick test, locomotor stimulation, and convulsive behavior. The second goal of this study was to determine whether acetylcodeine would alter the convulsant effects of diacetylmorphine. The antinociceptive potencies of acetylcodeine and codeine were similar, as reflected by their ED50 (95% confidence limits) values of 35 (29-44) and 51 (40-65) micromol/kg, respectively. Acetylcodeine was somewhat less potent than codeine in stimulating locomotor behavior, with ED50 values of 28 (22-37) and 12 (6-24) micromol/kg, respectively. Diacetylmorphine was considerably more potent than the other two drugs, producing antinociception and locomotor stimulation at ED50 values of 2.4 (1.4-4.1) and 0.65 (0.36-1.2) micromol/kg, respectively. On the other hand, the convulsant effects of acetylcodeine (ED50=138 (121-157) micromol/kg) and diacetylmorphine (ED50=115 (81-163) micromol/kg) were similar in potency and both were more potent than codeine (ED50=231 (188-283) micromol/kg). Finally, a subthreshold dose of acetylcodeine (72 micromol/kg) decreased the convulsant ED50 dose of diacetylmorphine to 40 (32-49). These findings suggest that the convulsant effects of acetylcodeine are more potent than predicted by its effects on locomotor activity and antinociception. The observation that acetylcodeine potentiated the convulsant effects of diacetylmorphine suggests a mechanism for some of the heroin-related deaths reported in human addicts." [Abstract]

Gilbert PE, Martin WR.
Antagonism of the convulsant effects of heroin, d-propoxyphene, meperidine, normeperidine and thebaine by naloxone in mice.
J Pharmacol Exp Ther. 1975 Mar;192(3):538-41.
"Naloxone antagonized convulsions produced by tail vein infusions of d-propoxyphene, heroin, meperidine, normeperidine and thebaine in mice in a dose-related manner. Pretreatment with naloxone (60 mg/kg i.p.) produced a 200 percent increase of the dose of d-propoxyphene or heroin needed to produce a seizure. A 40 percent increase in the convulsant dose of meperidine was observed after naloxone pretreatment (30 mg/kg i.p.). Naloxone (15 mg/kg i.p.) produced a 30 percent increase in the convulsant dose of normeperidine; however, larger doses of naloxone did not produce any further increase in the convulsant dose of either normeperidine or meperidine. Larger doses of naloxone were needed to antagonize convulsions produced by thebaine. Heroin, d-propoxyphene and meperidine produced nonlethal clonic seizures, whereas normeperidine and thebaine produced tonic-clonic seizures which were followed by death. These data suggest that there may be two mechanisms by which narcotic analgesics and their congeners produce convulsions." [Abstract]

Rady, Jodie J., Holmes, Blythe B., Portoghese, Philip S., Fujimoto, James M.
Morphine Tolerance in Mice Changes Response of Heroin from {micro} to {delta} Opioid Receptors
Proc Soc Exp Biol Med 2000 224: 93-101
"Heroin produced antinociception in the tail flick test through mu receptors in the brain of ICR and CD-1 mice, a response inhibited by 3-O-methylnaltrexone. Tolerance to morphine was produced by subcutaneous morphine pellet implantation. By the third day, the heroin response was produced through delta opioid receptors. The response was inhibited by simultaneous intracerebroventricular (i.c. v.) administration of naltrindole, a delta opioid receptor antagonist. More specifically, delta1 rather than delta2 receptors were involved because 7-benzylidenenaltrexone, a delta1 receptor antagonist, inhibited but naltriben, a delta2 antagonist, did not. Also, antinociception produced by i.c.v. heroin was inhibited by intrathecal administration of bicuculline and picrotoxin consistent with the concept that delta1 receptors in the brain mediated the antinociceptive response through descending neuronal pathways to the spinal cord to activate GABAA and GABAB receptors rather than spinal alpha2-adrenergic and serotonergic receptors activated originally by the mu agonist action in naive mice. The mu response of 6-monoacetylmorphine, a metabolite of heroin, was changed by morphine pellet implantation to a delta2 response (inhibited by naltriben but not 7-benzylidenenaltrexone). The agonist action of morphine in these morphine-tolerant mice remained mu. Thus, the opioid receptor selectivity of heroin and 6-monoacetylmorphine in the brain is changed by production of tolerance to morphine. Such a change explains how morphine tolerant mice are not cross-tolerant to heroin." [Full Text]

Martin, Thomas J., Kim, Susy A., Cannon, David G., Sizemore, Glen M., Bian, Di, Porreca, Frank, Smith, James E.
Antagonism of delta 2-Opioid Receptors by Naltrindole-5'-isothiocyanate Attenuates Heroin Self-Administration but Not Antinociception in Rats
J Pharmacol Exp Ther 2000 294: 975-982
"delta-Opioid receptors have been implicated in reinforcement processes and antagonists are available that produce long-lasting and selective antagonism of delta-opioid receptors in vivo. This experiment assessed the contribution of delta-opioid receptors to the antinociceptive and reinforcing properties of heroin. The effects of the irreversible delta-antagonist naltrindole-5'-isothiocyanate (5'-NTII) were evaluated on heroin self-administration and hot-plate antinociception in rats. 5'-NTII (10 nmol i.c.v.) shifted the dose-response curve for heroin self-administration downward, increasing the A(50) values on the ascending and descending limbs by approximately 0.5 log units and decreasing the maximum by 33%. 5'-NTII (40 nmol i.c.v.) shifted both limbs of the heroin self-administration dose-effect curve 1.2 log units to the right and decreased the maximum by 90%. Heroin self-administration gradually returned to baseline levels over 7 or 17 days after administration of 10 or 40 nmol 5'-NTII, respectively. 5'-NTII (40 nmol i.c.v.) decreased the self-administration of 0.17 mg/infusion cocaine by 40% while having no effect on responding maintained by 0.33 or 0.67 mg/infusion. 5'-NTII attenuated the antinociceptive effects of deltorphin (delta(2)) in a dose-dependent manner while having no effect on antinociception elicited after i.c. v. administration of [D-Pen(2),D-Pen(5)]-enkephalin (delta(1)) or [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (mu). In addition, the antinociceptive effects of heroin were not significantly affected by 5'-NTII (40 nmol i.c.v.). Therefore, 5'-NTII can attenuate the reinforcing effects of heroin at doses that do not affect its antinociceptive effects. Long-acting delta(2)-opioid antagonists may be beneficial in the treatment of heroin dependence or as adjuncts to reduce the abuse liability of opioid analgesics." [Full Text]

Comer, SD, Hoenicke, EM, Sable, AI, McNutt, RW, Chang, KJ, De Costa, BR, Mosberg, HI, Woods, JH
Convulsive effects of systemic administration of the delta opioid agonist BW373U86 in mice
J Pharmacol Exp Ther 1993 267: 888-895
"A systemically active, nonpeptidic delta receptor-selective agonist, (+-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl) -3- hydroxybenzyl)-N,N-diethylbenzamide (BW373U86), produced a brief, nonlethal convulsion in mice. The behavioral pattern of convulsion produced by pentylenetetrazol was similar to that produced by systemic administration of BW373U86. Although several episodes of convulsion occurred with pentylenetetrazol, BWB373U86 produced a single, brief episode. Naltrexone (10.0 and 100 mg/kg) and naltrindole (1.0, 3.2 and 10.0 mg/kg), but not midazolam (0.32 mg/kg), produced dose-dependent rightward shifts in the potency of BW373U86 to induce a convulsion. A dose of 3.2 mg/kg of midazolam completely eliminated convulsions induced by BW373U86. Midazolam (0.32 and 3.2 mg/kg), but not naltrindole (3.2 and 32.0 mg/kg), produced parallel rightward shifts in the pentylenetrazol dose-effect curve. Pretreatment with a single injection of BW373U86 (3.2, 10.0, 32.0 or 100 mg/kg) produced a dose-related reduction in the capacity of BW373U86 to induce a second convulsion. Recovery of sensitivity to BW373U86 did not return to control levels for up to 2 weeks after pretreatment with a single injection of 32.0 mg/kg of BW373U86. Naltrindole (3.2 mg/kg) administered within 1 hr, but not at 2 hr, after a pretreatment dose of 10.0 mg/kg of BW373U86 prevented the refractoriness (tolerance) induced by the single dose of BW373U86. These data suggest that the convulsions as well as the tolerance induced by BW373U86 were initiated through delta opioid receptors." [Abstract]

Broom, Daniel C., Nitsche, Joshua F., Pintar, John E., Rice, Kenner C., Woods, James H., Traynor, John R.
Comparison of Receptor Mechanisms and Efficacy Requirements for delta -Agonist-Induced Convulsive Activity and Antinociception in Mice
J Pharmacol Exp Ther 2002 303: 723-729
"Delta-opioid receptor-selective agonists produce antinociception and convulsions in several species, including mice. This article examines two hypotheses in mice: 1) that antinociception and convulsive activity are mediated through the same type of delta-receptor and 2) that greater delta-agonist efficacy is required for antinociception than for convulsive activity. Delta-mediated antinociception was evaluated in the acetic acid-induced abdominal constriction assay, which involves a low-intensity noxious stimulus; convulsive activity was indicated as a mild tonic-clonic convulsive episode followed by a period of catalepsy. In delta-opioid receptor knockout mice [DOR-1(-/-)], the nonpeptidic delta-agonists (+/-)-4-[(R*)-[(2S*,5R*)-2,5-dimethyl-4-(2-propenyl)-1- piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide hydrochloride (BW373U86) and (+)-4-[(R)-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N, N-diethylbenzamide (SNC80) failed to produce convulsive behavior demonstrating the absolute involvement of DOR-1 in this effect. In NIH Swiss mice expressing delta-opioid receptors, BW373U86 produced both antinociception and convulsive activity. These effects were antagonized by the putative delta(1)-receptor-selective antagonist 7-benzylidenenaltrexone and the putative delta(2)-receptor-selective antagonist naltriben. Tolerance developed to both the convulsive and antinociceptive effects of BW373U86. Tolerance to the convulsive, but not the antinociceptive, effects of BW373U86 was largely prevented when the antagonist naltrindole was given 20 min after each dose of the agonist in a 3-day treatment paradigm. The convulsive action of BW373U86 was also less sensitive than the antinociceptive action to treatment with the irreversible delta-antagonist naltrindole isothiocyanate. Collectively, these data suggest that the convulsive and antinociceptive activities of delta-agonists are mediated through the same receptor but that the receptor reserve for delta-mediated convulsive activity is greater than for delta-mediated antinociceptive activity." [Full Text]

Broom, Daniel C., Guo, Li, Coop, Andrew, Husbands, Stephen M., Lewis, John W., Woods, James H., Traynor, John R.
BU48: A Novel Buprenorphine Analog That Exhibits delta -Opioid-Mediated Convulsions but Not delta -Opioid-Mediated Antinociception in Mice
J Pharmacol Exp Ther 2000 294: 1195-1200
"N-Cyclopropylmethyl-[7alpha,8alpha,2', 3']-cyclohexano-1'[S]-hydroxy-6,14-endo-ethenotetrahydronororip avine (BU48) is a novel, ring-constrained analog of buprenorphine. In vivo, BU48 (0.1-10 mg/kg s.c.) produced brief, nonlethal convulsions in mice followed by brief Straub tail and a short period of catalepsy characteristic of BW373U86 and other nonpeptidic delta-receptor agonists. BU48-induced convulsions were sensitive to antagonism by naltrindole (10 mg/kg s.c.) and were also prevented by administration of the putative delta(1) antagonist 7-benzylidenenaltrexone and the putative delta(2) antagonist naltriben, with the latter being more potent. In the abdominal stretch assay in the mouse, only low-efficacy antinociceptive activity of BU48 (0.1-10 mg/kg) was seen. This was reversed by the kappa-opioid antagonist norbinaltorphimine (32 mg/kg s.c.) but not by the delta-opioid antagonist naltrindole (10 mg/kg s.c.). BU48 (10 mg/kg s.c.) acted as a delta-antagonist in this assay. In mouse brain homogenates, BU48 had high (nanomolar) binding affinity for all three opioid receptors in the order mu > delta = kappa. In vitro, the compound acted as a potent (EC(50) = 1.4 nM) kappa-opioid agonist in the guinea pig ileum and a potent (EC(50) = 0.2 nM) delta-opioid agonist in the mouse vas deferens but showed partial agonist activity at the rat cloned delta-opioid (40%) and human cloned kappa-opioid (59%) receptors with very low efficacy at the rat cloned mu-opioid receptor (10%); findings consistent with its in vivo profile. BU48 is the first described compound that produces delta-opioid-mediated convulsions without any evidence of delta-opioid-mediated antinociception and will be a useful tool in investigations of the delta-opioid receptor." [Full Text]

Khavandgar S, Homayoun H, Dehpour AR.
The role of nitric oxide in the proconvulsant effect of delta-opioid agonist SNC80 in mice.
Neurosci Lett. 2002 Aug 30;329(2):237-9.
"The involvement of nitric oxide (NO) in modulation of seizure susceptibility by delta-opioid agonist (+)-4-((alpha R)-alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC80) was examined in mice. Systemic administration of SNC80 (0.1-5 mg/kg, intraperitoneally (i.p.)) decreased the threshold for clonic seizures induced by pentylenetetrazole. The non-specific NO synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (3-20 mg/kg, i.p.), but not the specific inducible NOS inhibitor, aminoguanidine (50 and 100 mg/kg, i.p.) inhibited the proconvulsant effect of SNC80. On the other hand, NO substrate, L-arginine (30 and 60 mg/kg, i.p.) potentiated the proconvulsant effect of a lower dose of SNC80 (0.5 mg/kg). These results support the involvement of NO, produced by constitutive NOS, in the proconvulsant effect of the delta-opioid agonist." [Abstract]

Narayanaswami K.
Parameters for determining the origin of illicit heroin samples.
Bull Narc. 1985 Jan-Mar;37(1):49-62.
"A method has been evolved for assigning the source of supply or origin of illicit heroin samples. The content of morphine, codeine and acetyl products and the ratios of morphine to codeine and heroin to acetylcodeine obtained from opium samples of known origin as well as the content of heroin (diacetylmorphine) and acetylcodeine and their ratios in illicit heroin samples that have been found to belong to the same source of supply as the known opium samples are used as the basic criteria for a comparison to determine the origin of illicit heroin samples. Because the content of alkaloids in opium and heroin samples varies considerably, the number of opium and illicit heroin samples of known origin analysed should be sufficient to determine a representative composition of alkaloids in such samples for a given geographical area and period of production. It was observed that the theoretical ratio of heroin to acetylcodeine increases two-fold at each stage of the chemical conversion in the series opium-morphine-heroin. The ratios of heroin to acetylcodeine obtained from opium samples of known origin showed significant variation, which enabled the author to make distinct composition profiles of the alkaloids for each geographical area studied. Such profiles made it possible to compare heroin samples of known origin with illicit heroin samples of unknown origin and to determine the geographical area from which the latter originated. This method can also be applied in determining the origin of illicit morphine samples." [Abstract]

Girod C, Staub C.
Acetylcodeine as a marker of illicit heroin in human hair: method validation and results of a pilot study.
J Anal Toxicol. 2001 Mar;25(2):106-11.
"Acetylcodeine (AC), which is an impurity of illicit heroin synthesis, was suggested as a marker of heroin abuse. A procedure for simultaneous quantitation of 6-monoacetylmorphine (6-MAM), which is the major metabolite of heroin, morphine, codeine, and AC in hair was developed. Fifty-milligram hair samples were incubated in 0.01 M HCl overnight at 60 degrees C. The resulting hydrolyzed solutions were extracted by an automated solid-phase extraction procedure and drugs were analyzed by gas chromatography-mass spectrometry in selected ion monitoring mode (SIM). This required prior derivatization with propionic anhydride. Different validation parameters, such as linearity, intra-assay accuracy, extraction recoveries, and limit of quantitation, were described. Seventy-three hair samples from heroin abusers and 43 hair samples from subjects who had completed a heroin-maintenance program were analyzed. AC was detected in 92% of the first sample group and in only 12% of the second sample group. In the two groups, about 98% of AC-positive samples were found. These results prove that AC can be considered as a suitable marker of illicit heroin use, along with 6-MAM detection." [Abstract]
Christian Staub, Miguel Marset, Annie Mino, and Patrice Mangin
Detection of Acetylcodeine in Urine as an Indicator of Illicit Heroin Use: Method Validation and Results of a Pilot Study
Clin Chem 2001 47: 301-307.
"BACKGROUND: Acetylcodeine (AC), an impurity of illicit heroin synthesis, has been suggested as an interesting biomarker of illicit heroin use. METHODS: Procedures were developed for quantification of (a) morphine, 6-monoacetylmorphine (6-AM), and codeine in urine and (b) diacetylmorphine and AC in urine. Solid-phase extraction of the analytes was performed, and the extracted analytes were analyzed by selected-ion monitoring with gas chromatography-mass spectrometry. This procedure required prior derivatization with propionic anhydride. RESULTS: Different validation parameters were determined, such as linearity, reproducibility, extraction recoveries, and cutoffs. Seventy-one urine specimens of illicit heroin abusers and 44 urine specimens of subjects in a heroin maintenance program were analyzed. AC was detected in 85.9% of the samples of the first group but not in any of the samples from subjects taking medical heroin. In the two groups, there were 94.4% and 84.1% 6-AM positive urine specimens, respectively. Detection times were determined for AC and codeine by parallel administration of heroin containing various percentages of AC to four voluntary patients in a heroin maintenance program. The measured detection times were 8 and 23 h for AC and codeine, respectively. CONCLUSIONS: These results indicate that, together with detection of 6-AM in urine, AC is a suitable marker of illicit heroin use." [Abstract]
Bogusz MJ, Maier RD, Erkens M, Kohls U.
Detection of non-prescription heroin markers in urine with liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.
J Anal Toxicol. 2001 Sep;25(6):431-8.
"The planned introduction of a prescription heroin program in Germany created a need for differentiation between non-prescription and prescribed diamorphine use. The following substances were chosen as markers of non-prescription heroin: acetylcodeine (AC); its metabolites codeine (C) and codeine 6-glucuronide (C6G); papaverine (P); and noscapine (N). Typical heroin markers diamorphine (DAM) and its metabolites monoacetylmorphine (MAM) and morphine (M) were also determined. The drugs were extracted from urine samples with solid-phase extraction (C18) using standard 200-mg columns and 96-well microplates (100 mg). The extracts were examined with liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (positive ionization) in two isocratic systems. Selected ion monitoring procedures were applied for protonated molecular masses and characteristic fragments of drugs involved. The limits of detection were in the range of 0.5-1 ng/mL urine. The occurrence of selected heroin markers was investigated in 25 urine samples collected from heroin abusers (road traffic offenders and overdosed patients). C6G was found in all samples, C in 24 samples, N in 22 samples, MAM in 16 samples, P in 14 samples, DAM in 12 samples, and AC in 4 samples. The appearance of these compounds in urine reflects their pharmacokinetic properties and the composition of non-prescription heroin." [Abstract]
Brenneisen R, Hasler F.
GC/MS determination of pyrolysis products from diacetylmorphine and adulterants of street heroin samples.
J Forensic Sci. 2002 Jul;47(4):885-8.
"The inhalation of heroin vapors after heating on aluminium foil ("chasing the dragon") is gaining popularity nowadays among heroin users seeking to avoid the risks of parenteral drug administration. The heroin-smoking procedure was simulated under laboratory conditions by heating the samples on aluminium foil at 250 to 400 degrees C and collecting the vapors in a condenser trap. A total of 72 pyrolysis products of diacetylmorphine, street heroin, residues from aluminium foils used to smoke street heroin, typical by-products, and adulterants were detected by gas chromatography/mass spectrometry (GC/MS). About half of these compounds could be identified. Diacetylmorphine (base and salt) undergoes substantial to complete degradation. Some typical street heroin constituents, like morphine, codeine, acetylcodeine, papaverine, and caffeine, are rather heat-stable. Other compounds, like noscapine and paracetamol, are pyrolyzed to a greater extent. The principal chemical reactions leading to the formation of pyrolysis products are desacetylation, transacetylation, N-demethylation, O-methylation, ring cleavage and oxydation." [Abstract]

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Recent Acetylcodeine Research
1) Zhang JX, Chen CY
A rapid method for profiling samples of illicit heroin.
Drug Test Anal. 2012 Jun;4(6):530-3.
The aim of this investigation was to profile samples of illicit heroin. It involved derivatization and gas chromatographic separation followed by a fully automated data analysis. Six major constituents (acetylcodeine, 6-monoacetylmorphine, papaverine, noscapine, codeine, and morphine) were tested and analyzed. The square cosine function was used to evaluate correlation values. The method proved to be efficient and reliable providing information on links between illicit heroin samples. Copyright � 2012 John Wiley & Sons, Ltd. [PubMed Citation] [Order full text from Infotrieve]

2) Sun YY, Xiang P, Shen M
[Simultaneous determination of 11 opiates in hair by liquid chromatography-tandem mass spectrometry].
Yao Xue Xue Bao. 2011 Dec;46(12):1501-6.
The paper reports the establishment of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneous analysis of 11 opiates in hair samples, and the study of presence of opiates in the hair of active heroin addicts. About 20 mg of decontaminated and pulverized hair sample was hydrolyzed with buffer solution for 30 min, in the presence of morphine-d3 and acetylmorphine-d6 used as internal standards, and then extracted with the mixture of dichlormethane and isopropanol, separated by the Allure PFP propyl column with a mobile phase consisting of acetonitrile and 20 mmol L(-1) ammonium acetate buffer, and then analyzed by LC-MS/MS. Multiple reaction monitoring (MRM) mode was used to analyze 11 opiates. Eleven opiates showed a fairly good linearity over the corresponding range (r > 0.996 0). The detection limits were less than 0.05 ng mg(-1). The recoveries were between 47.2% and 110%, and the deviations of intra- and inter-day precision were less than 14%. Heroin, acetylmorphine, morphine, codeine, acetylcodeine and hydrocodone were detected in hair samples of 21 herion addicts. The developed method shows high sensitivity and selectivity, and is suitable for the simultaneous analysis of 11 opiates in hair samples and identify legal and illegal use of opiates. [PubMed Citation] [Order full text from Infotrieve]

3) Chan KW, Tan GH, Wong RC
Gas chromatographic method validation for the analysis of major components in illicit heroin seized in Malaysia.
Sci Justice. 2012 Mar;52(1):9-16.
Apart from routine analysis of total morphine content required by the criminal justice system, quantification of other major components in illicit heroin has not been considered by the Malaysian enforcement laboratory. In order to quantify various other cutting agents in addition to alkaloids, a gas chromatographic (GC) method was developed to facilitate simultaneous quantification of eight target analytes commonly found in illicit heroin seized in Malaysia within a 12 min run time. The validation results demonstrated high selectivity with the use of an HP Ultra 2 capillary column. Different solvents were studied and methanol:chloroform (1:9) proved best for sample dissolution. The method was repeatable and reproducible. The study ranges covering 50-150% of the preferred concentrations of the eight analytes obtained r(2)>0.9997. Limits of detection up to 6?g/mL were also obtained and the method achieved 99-102% recovery. The capability of the method in heroin profiling was verified using samples from ten case samples. [PubMed Citation] [Order full text from Infotrieve]

4) Cone EJ
Oral fluid results compared to self reports of recent cocaine and heroin use by methadone maintenance patients.
Forensic Sci Int. 2012 Feb 10;215(1-3):88-91.
[PubMed Citation] [Order full text from Infotrieve]

5) Zeng J, Zou J, Song X, Chen J, Ji J, Wang B, Wang Y, Ha J, Chen X
A new strategy for basic drug extraction in aqueous medium using electrochemically enhanced solid-phase microextraction.
J Chromatogr A. 2011 Jan 14;1218(2):191-6.
This work describes an electrochemically enhanced solid-phase microextraction (EE-SPME) method using a mild negative potential (-0.6 V) for the enhanced extraction of the selected basic drugs in a pure aqueous matrix and urine samples. The EE-SPME method gave a more effective extraction of drugs (primarily via electrophoresis and complementary charge interaction) compared to that obtained with SPME (without applying a potential, and which is based on passive partitioning). The EE-SPME method eliminated the need for alkalizing, derivatizing the drugs, or modifying the fiber coating before extraction. The analysis of methamphetamine (MA) and amphetamine (AM) was selected as a typical example to demonstrate in detail the advantages of EE-SPME over SPME. Based on the results obtained, 3-min extraction efficiency for both the amphetamines using EE-SPME was better than that of 30-min using SPME. The developed EE-SPME-GC method exhibited wide linear ranges (2-1000 ng mL(-1)) for both the amphetamines with R(2) larger than 0.99, and the method detection limits (MDLs) for AM and MA were 0.26 and 0.12 ng mL(-1), respectively. In addition, the EE-SPME method developed was also successfully applied to enhance the extraction of several other basic drugs (ephedrine, 3,4-methylenedioxyamphetamine (MDA), atropine, methadone, cocaine, codeine, acetylcodeine and papaverine) with preconcentration factors from 157 to 2199, indicating the potential applicability of this method in the field of forensic, clinical and pharmaceutical analysis. [PubMed Citation] [Order full text from Infotrieve]

6) Concheiro M, Shakleya DM, Huestis MA
Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry.
Anal Bioanal Chem. 2011 Apr;400(1):69-78.
A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3'-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1-1,000 ng/patch, except EME 5-1,000 ng/patch. Intra-, inter-day and total imprecision were <10.1%CV, analytical recovery 87.2-107.7%, extraction efficiency 35.3-160.9%, and process efficiency 25.5-91.7%. Ion suppression was detected for EME (-63.3%) and EDDP (-60.4%), and enhancement for NBUP (42.6%). Deuterated internal standards compensated for these effects. No carryover was detected, and all analytes were stable for 24 h at 22 �C, 72 h at 4 �C, and after three freeze/thaw cycles. The method was applied to weekly sweat patches from an opioid-dependent BUP-maintained pregnant woman; 75.0% of sweat patches were positive for BUP, 93.8% for cocaine, 37.5% for opiates, 6.3% for methadone and all for tobacco biomarkers. This method permits a fast and simultaneous quantification of 14 drugs and metabolites in sweat patches, with good selectivity and sensitivity. [PubMed Citation] [Order full text from Infotrieve]

7) Zhang J, Meng P, Zhang D, Zhang W, Chen C
[Analysis on opioid compounds in the hair of heroin addicts with LC-MS/MS].
Wei Sheng Yan Jiu. 2010 Sep;39(5):593-6.
[PubMed Citation] [Order full text from Infotrieve]

8) Concheiro M, Gray TR, Shakleya DM, Huestis MA
High-throughput simultaneous analysis of buprenorphine, methadone, cocaine, opiates, nicotine, and metabolites in oral fluid by liquid chromatography tandem mass spectrometry.
Anal Bioanal Chem. 2010 Sep;398(2):915-24.
A method for simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), anhydroecgonine methyl ester (AEME), morphine, codeine, 6-acetylmorphine (6AM), heroin, 6-acetylcodeine (6AC), nicotine, cotinine, and trans-3'-hydroxycotinine (OH-cotinine) by liquid chromatography tandem mass spectrometry in oral fluid (OF) was developed and extensively validated. Acetonitrile (800 ?L) and OF (250 ?L) were added to a 96-well Isolute-PPT+protein precipitation plate. Reverse-phase separation was achieved in 16 min and quantification was performed by multiple reaction monitoring. The assay was linear from 0.5 or 1 to 500 ?g/L. Intraday, interday, and total imprecision were less than 13% (n?=?20), analytical recovery was 92-114% (n?=?20), extraction efficiencies were more than 77% (n?=?5), and process efficiencies were more than 45% (n?=?5). Although ion suppression was detected for EME, cocaine, morphine, 6AC, and heroin (less than 56%) and enhancement was detected for BE and nicotine (less than 316%), deuterated internal standards compensated for these effects. The method was sensitive (limit of detection 0.2-0.8 ?g/L) and specific (no interferences) except that 3-hydroxy-4-methoxyamphetamine interfered with AEME. No carryover was detected, and all analytes were stable for 24 h at 22 �C, for 72 h at 4 �C, and after three freeze-thaw cycles, except cocaine, 6AC, and heroin (22-97% loss). The method was applied to 41 OF specimens collected throughout pregnancy with a Salivette� OF collection device from an opioid-dependent BUP-maintained pregnant woman. BUP ranged from 0 to 7,400 ?g/L, NBUP from 0 to 71 ?g/L, methadone from 0 to 3 ?g/L, nicotine from 32 to 5,020 ?g/L, cotinine from 125 to 508 ?g/L, OH-cotinine from 11 to 51 ?g/L, cocaine from 0 to 419 ?g/L, BE from 0 to 351 ?g/L, EME from 0 to 286 ?g/L, AEME from 0 to 7 ?g/L, morphine from 0 to 22 ?g/L, codeine from 0 to 1 ?g/L, 6AM from 0 to 4 ?g/L, and heroin from 0 to 2 ?g/L. All specimens tested negative for EDDP and 6AC. This method permits a fast and simultaneous quantification of 16 drugs and metabolites in OF, with good selectivity and sensitivity. [PubMed Citation] [Order full text from Infotrieve]

9) Barroso M, Dias M, Vieira DN, L�pez-Rivadulla M, Queiroz JA
Simultaneous quantitation of morphine, 6-acetylmorphine, codeine, 6-acetylcodeine and tramadol in hair using mixed-mode solid-phase extraction and gas chromatography-mass spectrometry.
Anal Bioanal Chem. 2010 Apr;396(8):3059-69.
A simple procedure has been developed and validated for the qualitative and quantitative analysis of several opiates (morphine, 6-acetylmorphine, codeine, 6-acetylcodeine) and tramadol in hair. The analytes were extracted from within the matrix via an overnight incubation with methanol at 65 degrees C, and afterwards the samples were cleaned up by mixed-mode solid-phase extraction. The extracts were derivatized with N-methyl-N-(trimethylsilyl) trifluoroacetamide with 5% trimethylchlorosilane and analyzed by gas chromatography-mass spectrometry in the selected ion monitoring mode. The method was linear from 0.05 (lower limit of quantitation) to 50 ng/mg (40 ng/mg for tramadol), with correlation coefficients higher than 0.99 for all compounds, accomplishing the cut-off values proposed by the Society of Hair Testing for the detection of these substances in hair (0.2 ng/mg). Intra- and interday precision and trueness were in conformity with the criteria normally accepted in bioanalytical method validation, and the sample cleanup step presented a mean efficiency higher than 90% for all analytes. Furthermore, using these incubation conditions, 6-acetylmorphine did not significantly hydrolyze to morphine. For these reasons, and because of its simplicity, the proposed method can be successfully applied in the determination of these compounds in hair samples, and is suitable for application in routine analysis with forensic purposes. [PubMed Citation] [Order full text from Infotrieve]

10) Shakleya DM, Dams R, Choo RE, Jones H, Huestis MA
Simultaneous liquid chromatography-mass spectrometry quantification of urinary opiates, cocaine, and metabolites in opiate-dependent pregnant women in methadone-maintenance treatment.
J Anal Toxicol. 2010 Jan-Feb;34(1):17-25.
Opiates, cocaine, and metabolites were quantified by liquid chromatography-mass spectrometry (LC-MS) in 284 urine specimens, collected thrice weekly, to monitor possible drug relapse in 15 pregnant heroin-dependent women. Opiates were detected in 149 urine specimens (52%) with limits of quantification (LOQ) of 10-50 microg/L. Morphine, morphine-3-glucuronide, and/or morphine-6-glucuronide were positive in 121 specimens; 6-acetylmorphine, a biomarker of heroin ingestion, was quantifiable in only 7. No heroin, 6-acetylcodeine, papaverine, or noscapine were detected. One hundred and sixty-five urine specimens (58%) from all 15 participants were positive for one or more cocaine analytes (LOQ 10-100 microg/L). Ecgonine methylester (EME) and/or benzoylecgonine were the major cocaine biomarkers in 142. Anhydroecgonine methylester, a biomarker of smoked cocaine, was positive in six; cocaethylene and/or ecgonine ethylester, biomarkers of cocaine and ethanol co-ingestion, were found in 25. At the current Substance Abuse Mental Health Services Administration cutoffs for total morphine (2000 microg/L), codeine (2000 microg/L), 6-acetylmorphine (10 microg/L), and benzoylecgonine (100 microg/L), 16 opiate- and 29 cocaine-positive specimens were identified. Considering 100 microg/L EME as an additional urinary cocaine biomarker would identify 51 more positive cocaine specimens. Of interest is the differential pattern of opiate and cocaine biomarkers observed after LC-MS as compared to gas chromatography-mass spectrometry analysis. [PubMed Citation] [Order full text from Infotrieve]

11) Fritch D, Blum K, Nonnemacher S, Haggerty BJ, Sullivan MP, Cone EJ
Identification and quantitation of amphetamines, cocaine, opiates, and phencyclidine in oral fluid by liquid chromatography-tandem mass spectrometry.
J Anal Toxicol. 2009 Nov-Dec;33(9):569-77.
Analytical methods for measuring multiple licit and illicit drugs and metabolites in oral fluid require high sensitivity, specificity, and accuracy. With the limited volume available for testing, comprehensive methodology is needed for simultaneous measurement of multiple analytes in a single aliquot. This report describes the validation of a semi-automated method for the simultaneous extraction, identification, and quantitation of 21 analytes in a single oral fluid aliquot. The target compounds included are amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-amphetamine, 3,4-methylenedioxyethylamphetamine, pseudoephedrine, cocaine, benzoylecgonine, codeine, norcodeine, 6-acetylcodeine, morphine, 6-acetylmorphine, hydrocodone, norhydrocodone, dihydrocodeine, hydromorphone, oxycodone, noroxycodone, oxymorphone, and phencyclidine. Oral fluid specimens were collected with the Intercept device and extracted by solid-phase extraction (SPE). Drug recovery from the Intercept device averaged 84.3%, and SPE extraction efficiency averaged 91.2% for the 21 analytes. Drug analysis was performed by liquid chromatography-tandem mass spectrometry in the positive electrospray mode using ratios of qualifying product ions within +/-25% of calibration standards. Matrix ion suppression ranged from -57 to 8%. The limit of quantitation ranged from 0.4 to 5 ng/mL using 0.2 mL of diluted oral fluid sample. Application of the method was demonstrated by testing oral fluid specimens from drug abuse treatment patients. Thirty-nine patients tested positive for various combinations of licit and illicit drugs and metabolites. In conclusion, this validated method is suitable for simultaneous measurement of 21 licit and illicit drugs and metabolites in oral fluid. [PubMed Citation] [Order full text from Infotrieve]

12) Brunet BR, Barnes AJ, Choo RE, Mura P, Jones HE, Huestis MA
Monitoring pregnant women's illicit opiate and cocaine use with sweat testing.
Ther Drug Monit. 2010 Feb;32(1):40-9.
Dependence on illicit drugs during pregnancy is a major public health concern as there may be associated adverse maternal, fetal, and neonatal consequences. Sweat patches (n = 389) were collected from 39 pregnant volunteers who provided written informed consent for this Institutional Review Board-approved protocol and wore patches, replaced approximately weekly, from study entry until delivery. Patches were analyzed for opiates (heroin, 6-acetylmorphine, 6-acetylcodeine, morphine and codeine) and cocaine (cocaine, benzoylecgonine, ecgonine methyl ester, anhydroecgonine methyl ester) by solid phase extraction and gas chromatography mass spectrometry. Seventy-one percent (276) of collected sweat patches were > or =5 ng per patch (limit of quantification) for one or more analytes. Cocaine was present in 254 (65.3%) patches in concentrations ranging from 5.2 to 11,835 ng per patch with 154 of these high enough to satisfy the proposed Substance Abuse and Mental Health Services Administration guidelines for a confirmatory drug test (25 ng per patch). Interestingly, 6-acetylmorphine was the most prominent opiate analyte documented in 134 patches (34.4%) with 11.3% exceeding the proposed opiate Substance Abuse and Mental Health Services Administration cut-off (25 ng per patch). Heroin was identified in fewer patches (77), but in a similar concentration range (5.3-345.4 ng per patch). Polydrug use was evident by the presence of both cocaine and opiate metabolites in 136 (35.0%) patches. Sweat testing is an effective method for monitoring abstinence or illicit drug use relapse in this high-risk population of pregnant opiate- and/or cocaine-dependent women. [PubMed Citation] [Order full text from Infotrieve]

13) Musshoff F, Trafkowski J, Lichtermann D, Madea B
Comparison of urine results concerning co-consumption of illicit heroin and other drugs in heroin and methadone maintenance programs.
Int J Legal Med. 2010 Sep;124(5):499-503.
Urine samples of patients from a heroin maintenance program (HMP) and a methadone maintenance program (MMP) were chromatographically analyzed 1 month before and 6 and 12 months into treatment for the presence of classical markers of heroin use as well as for the presence of markers for illicit heroin abuse. Furthermore, the samples were immunochemically tested for cannabinoids, cocaine metabolites, amphetamine, methylendioxyamphetamines and benzodiazepines. A co-consumption of illicit heroin (HER) in the HMP was determined to be 50% but was significantly lower compared to the MMP with a co-use of 71%. The incidence was high because not only acetylcodeine (AC) as a very specific marker was considered but also other marker substances for illicit HER use. Amphetamines played only a minor part in both collectives, and the proportion of HER and methadone patients using cocaine was similar and decreased during treatment. Also, the benzodiazepine use decreased, and cannabis use was high in both collectives during treatment. Considering only the AC in the present study, a co-use of illicit HER in the HMP was similar to previous reports concerning HER-assisted treatment programs. If additional marker substances were examined, the suspicion of a co-use of illicit HER is markedly enhanced. [PubMed Citation] [Order full text from Infotrieve]

14) Liu YM, Tian W, Jia YX, Yue HY
The use of CE ECL with ionic liquid for the determination of drug alkaloids and applications in human urine.
Electrophoresis. 2009 Apr;30(8):1406-11.
A new approach for the determination of methylephedrine hydrochloride (ME), thebaine, codeine phosphate (CP), and acetylcodeine (AC) was established by CE-ECL with ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate). The conditions for the CE separation, ECL detection, and the effect of ionic liquid were systematically investigated. Under the optimal conditions, the four analytes were well separated within 8 min using 1-butyl-3-methylimidazolium tetrafluoroborate as additive in the electrophoretic buffer. The concentration detection limits of ME, thebaine, CP, and AC were 2.1 x 10(-8), 1.4 x 10(-7), 6.3 x 10(-8), and 3.6 x 10(-8) mol/L (S/N=3), respectively. The LOQs (S/N=10) in real human urine samples were 7.6 x 10(-7) mol/L for ME, 3.6 x 10(-6) mol/L for thebaine, 6.5 x 10(-7) mol/L for CP, and 4.6 x 10(-7) mol/L for AC, respectively. The recoveries of four alkaloids at different levels in human urine samples were between 90.0 and 103.5%. The developed method was successfully applied to the determination of four drug alkaloids in human urine samples. [PubMed Citation] [Order full text from Infotrieve]

15) Zhang Z, Yan B, Liu K, Bo T, Liao Y, Liu H
Fragmentation pathways of heroin-related alkaloids revealed by ion trap and quadrupole time-of-flight tandem mass spectrometry.
Rapid Commun Mass Spectrom. 2008 Sep;22(18):2851-62.
The electrospray ionization (ESI) ion trap and quadrupole time-of-flight (QqToF) mass spectra of heroin and seven related alkaloids, i.e., morphine, codeine, O-6-monoacetylmorphine (6-MAM), thebaine, acetylcodeine, papaverine and narcotine, have been extensively investigated in this work. The ESI mass spectrometric fragmentation pathways of protonated 6-MAM, heroin, acetylcodeine, and thebaine were comprehensively elucidated for the first time with the aid of high-resolution mass spectrometry. It was found that cleavage of the piperidine ring was the featured fragmentation route of six of the compounds, although not of papaverine and narcotine. In addition, a simple high-performance liquid chromatography (HPLC)-based separation method gave baseline resolution of all eight components. This study could play an important role in the screening for these alkaloids in different matrices by HPLC coupled to tandem mass spectrometry (MS/MS). [PubMed Citation] [Order full text from Infotrieve]

16) Musshoff F, Lachenmeier K, Lichtermann D, Madea B
Cocaine and opiate concentrations in hair from subjects in a heroin maintenance program in comparison to a methadone substituted group.
Int J Legal Med. 2009 Sep;123(5):363-9.
One month before (T-1) and 12 months after (T12) controlled i.v. administration of pharmaceutical heroin-HCl (10-100 mg/day) in the context of a heroin maintenance program (HMP), concentrations of opiates and cocaine as well as its metabolites were determined in head hair (n = 46) using a validated gas chromatographic-mass spectrometric method. In addition, a patient collective of a methadone maintenance program (MMP, daily doses 15-260 mg) was examined (n = 35). The incidence of additional cocaine consumption decreased in both groups during the study period (T-1 to T12): in HMP from 64.6% to 45.8% and in MMP from 71.4% to 60.0%. A significant reduction of cocaine consumption was defined as an at least 30% reduction of analyte concentrations in hair (Deltac > 30%). Accordingly, in HMP, a decrease in 45.8% of initially (T-1) cocaine-positive patients was determined; in MMP, the reduction was 48.6%. In 22.9% of HMP and 37.1% of MMP, an increase of cocaine concentrations was detected. Codeine and acetylcodeine were found in 50.0% and 43.5% (T-1) and 13.0% and 10.9% (T12) of the samples of the HMP, as well as in 45.7% and 25.7% (T-1) and 17.1% and 5.7% (T12) in MMP, respectively. The missing of acetylcodeine, in particular at T-1, questions its applicability as a characteristic marker of a preceding consumption of illicit heroin in hair analysis. [PubMed Citation] [Order full text from Infotrieve]

17) Brunet BR, Barnes AJ, Scheidweiler KB, Mura P, Huestis MA
Development and validation of a solid-phase extraction gas chromatography-mass spectrometry method for the simultaneous quantification of methadone, heroin, cocaine and metabolites in sweat.
Anal Bioanal Chem. 2008 Sep;392(1-2):115-27.
A sensitive and specific method is presented to simultaneously quantify methadone, heroin, cocaine and metabolites in sweat. Drugs were eluted from sweat patches with sodium acetate buffer, followed by SPE and quantification by GC/MS with electron impact ionization and selected ion monitoring. Daily calibration for anhydroecgonine methyl ester, ecgonine methyl ester, cocaine, benzoylecgonine (BE), codeine, morphine, 6-acetylcodeine, 6-acetylmorphine (6AM), heroin (5-1000 ng/patch) and methadone (10-1000 ng/patch) achieved determination coefficients of >0.995, and calibrators quantified to within +/-20% of the target concentrations. Extended calibration curves (1000-10,000 ng/patch) were constructed for methadone, cocaine, BE and 6AM by modifying injection techniques. Within (N = 5) and between-run (N = 20) imprecisions were calculated at six control levels across the dynamic ranges with coefficients of variation of <6.5%. Accuracies at these concentrations were +/-11.9% of target. Heroin hydrolysis during specimen processing was <11%. This novel assay offers effective monitoring of drug exposure during drug treatment, workplace and criminal justice monitoring programs. [PubMed Citation] [Order full text from Infotrieve]

18) Cone EJ, Clarke J, Tsanaclis L
Prevalence and disposition of drugs of abuse and opioid treatment drugs in oral fluid.
J Anal Toxicol. 2007 Oct;31(8):424-33.
Testing oral fluid for drugs of abuse has been studied under many conditions but rarely has been evaluated in large population databases. We evaluated oral fluid tests in a database from a commercial laboratory in the United Kingdom composed of 8679 confirmed positive results. The results originated from 635,000 specimens collected over the period of May 2004 through September 2006. Oral fluid specimens were collected with the Intercept oral fluid collection device, screened by enzyme immunoassay, and confirmed by GC-MS or GC-MS-MS. The database was organized by collection settings (legal/treatment, N = 8198 specimens; and workplace, N = 481 specimens) and by drug groups (without consideration of collection setting). The drug groups were as follows (number of confirmed positives): amphetamines (468); benzodiazepines (892); buprenorphine (276); cannabinoids (725); cocaine (1443); methadone (998); and opiates (5739). The goal of the study was to provide drug/metabolite prevalence data, concentrations, and drugs/metabolite patterns encountered in oral fluid. Comparison of results by collection setting indicated differences in relative frequency, primarily for opiates and cannabinoids. Opiate positives were most frequently observed for specimens collected in legal/treatment settings, whereas cannabinoids were most frequently reported in the workplace. An array of information on drug and metabolite occurrences and concentration arose from evaluation of the data by drug groups. Amphetamine was the predominant drug reported for the Amphetamines Group; approximately 10% were also positive for MDA and/or MDMA; and methamphetamine was rarely reported. Multiple combinations of diazepam, nordiazepam, oxazepam, temazepam, chlordiazepoxide, and lorazepam were reported for the Benzodiazepine Group. Buprenorphine, an opioid treatment drug, was the predominant analyte reported, but low concentrations of norbuprenorphine were frequently reported. THC was the predominant analyte reported in the Cannabinoids Group and was frequently reported in combination with cannabidiol and cannabinol. THCCOOH was reported in only 10.8% of these specimens and was never reported in the absence of THC. HO-THC was reported in 5.7% of the specimens. In the Cocaine Group, cocaine was present, often in combination with BZE, but also as the sole analyte in 17.3% of the specimens. AEME and cocaethylene were reported in 10.4% and 5.5% of the specimens. Methadone, another opioid treatment drug, was reported in all specimens for the Methadone Group; EDDP was reported in 30.1% of the specimens. In the Opiates Group, morphine, codeine and 6-acetylmorhine were most frequently reported, often in combination. The frequency of detection of 6-acetylmorphine when morphine was present (N = 4575 specimens) was 77.5%. Surprisingly, heroin (19.0%; N = 1091 specimens) and 6-acetylcodeine (24.9%; N = 1431 specimens) were frequently reported. The results from analysis of this large oral fluid database offer a rich mixture of new information on detection frequency, drug and metabolite patterns, and concentration data on drugs of abuse. [PubMed Citation] [Order full text from Infotrieve]

19) Al-Asmari AI, Anderson RA
Method for quantification of opioids and their metabolites in autopsy blood by liquid chromatography-tandem mass spectrometry.
J Anal Toxicol. 2007 Sep;31(7):394-408.
A method using liquid chromatography-electrospray ionization-tandem mass spectrometry was developed and validated for the determination of morphine, codeine, hydromorphone, dihydrocodeine, oxycodone, buprenorphine, and naloxone with their metabolites morphine-3-glucuronide, morphine-6-glucuronide, normorphine, 6-acetylmorphine, 6-acetylcodeine, codeine-6-glucuronide, norcodeine, hydromorphine-3-glucuronide, dihydrocodeine-6-glucuronide, dihydromorphine, dihydromorphine-3-glucuronide, dihydromorphine-6-glucuronide, oxymorphone, norbuprenorphine, buprenorphine-3-glucuronide, norbuprenorphine-3-glucuronide, and naloxone-3-glucuronide in human whole blood. Polar metabolites (glucuronides) and other analytes were extracted by SPE using Bond Elut C18. Chromatographic separation was performed on a Phenomenex Synergi reversed-phase column with gradient elution based on a mobile phase consisting of 10mM ammonium formate adjusted to pH 3 and acetonitrile. Intraday and interday precision for all analytes were between 0.6% and 13.8%, and recoveries were between 80.3% and 101.4%. Calibration curves were linear for all analytes over the concentration range 5-400 ng/mL, and correlation coefficients (R(2)) were better than 0.999. Limits of detection and quantitation were 0.16-1.2 ng/mL and 0.5-4.09 ng/mL, respectively. The method described consolidates previous work on opioids and their metabolites published in the literature and is the first to include the detection of naloxone-3-glucuronide. The method has been applied in routine postmortem cases after opiate overdose with the threefold purpose of providing interpretive information on the cause and type of death (rapid, sub-acute, or delayed death) and to distinguish heroin, morphine, and codeine users. [PubMed Citation] [Order full text from Infotrieve]

20) Soltaninejad K, Faryadi M, Akhgari M, Bahmanabadi L
Chemical profile of counterfeit buprenorphine vials seized in Tehran, Iran.
Forensic Sci Int. 2007 Oct 25;172(2-3):e4-5.
Buprenorphine, commonly known by the trademark Temgesic, is one of the most popular drugs of abuse among the opioid-addicted young individuals in Iran. Temgesic, Bungesic, etc. are the most popular and important illicit opioid drugs in Tehran's illicit drugs black market, and are now among the most widely abused by opioid addicts. Because of this, counterfeiting of this drug has increased in Tehran. In this study, the qualitative analysis of counterfeit buprenorphine by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) demonstrates the presence of diacetylmorphine, acetylcodeine and pheniramine, as well as the absence of buprenorphine. In conclusion, due to the absence of quality control and difficulties in differentiating counterfeit buprenorphine from genuine products, the use of counterfeit buprenorphine leads the opioid abusers to health risks. [PubMed Citation] [Order full text from Infotrieve]