Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam,Methadone, and Morphine

Postmortem redistribution (PMR) refers to the site‐ and time‐related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites. Intracardiac blood (ICB), subclavian blood (SB), femoral blood (FB), and popliteal blood (PB) were sampled in 30 cases. To assess PMR, mean concentrations and ratios were compared. Influence of postmortem interval on mean ratios was also assessed. Results show that popliteal mean concentrations were lower than those for other sites for all three drugs, even lower than femoral blood; mean ratios suggested that the popliteal site was less subject to PMR, and estimated postmortem interval did not influence ratios except for diazepam and methadone FB/PB. In conclusion, our study is the first to explore the popliteal site and suggests that popliteal blood is less prone to postmortem redistribution.     

Site‐, Technique‐, and Time‐Related Aspects of the Postmortem Redistribution of Diazepam,Methadone, Morphine,and their Metabolites: Interest of Popliteal Vein Blood Sampling

Sampling site, technique, and time influence postmortem drug concentrations. In 57 cases, we studied drug concentration differences as follows: subclavian vein‐dissection/clamping versus blind stick, femoral vein‐dissection/clamping versus blind stick, right cardiac chamber, and popliteal vein‐dissection and clamping only. Cases were distributed in group #1 (all cases with both techniques), group #2 (dissection/clamping), and group #3 (blind stick). Sampled drugs were diazepam, methadone, morphine, and their metabolites. To assess PMR, mean concentrations and ratios were calculated for each group. Time‐dependent variations of blood concentrations and ratios were also assessed. Results indicate that site, method, and time may influence postmortem distribution interpretation in different ways. Popliteal blood seems less subject to PMR. In conclusion, our study is the first to evaluate concurrently three main aspects of PMR and confirms that the popliteal vein may represent a site that is more resistant to the changes seen as a result of PMR.     

Quantitative structure–activity relationship (QSAR) methodology in forensic toxicology: Modeling postmortem redistribution of structurally diverse drugs using multivariate statistics

Postmortem redistribution (PMR) constitutes a multifaceted process, which renders the analytical results of drug concentrations inaccurate to be interpreted by forensic toxicologists. The aim of the present study was to evaluate whether quantitative structure–activity relationship (QSAR) methodology could serve as an effective tool to estimate the ability of drugs to redistribute across tissue barriers during postmortem period on the basis of their molecular, physicochemical and structural properties. In this aspect, multivariate data analysis (MVDA) was applied to a set of 77 structurally diverse drugs. PMR data expressed by the central:peripheral concentration ratio (C:P ratio) was taken from the literature. An adequate and robust QSAR model (R² = 0.65, Q² = 0.56, RMSEE = 0.34) was established for 59 (77%) out of 77 drugs. Although the derived QSAR model presented limited applicability, it provided an informative illustration of the contributing molecular, physicochemical and structural properties in PMR process. Drugs with strong basic properties and enhanced molecular size, flexibility, lipophilicity and number of halogens were found to be susceptible to increased PMR. Due to the high complexity of PMR process, further QSAR studies need to focus on structurally related drugs to develop more specific models, which could serve as alternative tools to evaluate PMR for different chemical classes.     

Unconjugated morphine in blood by radioimmunoassay and gas chromatography/mass spectrometry

Morphine, the active metabolite of heroin, is rapidly inactivated by glucuronidation at the 3 carbon. Unconjugated (pharmacologically active) morphine was measured in postmortem blood by radioimmunoassay using an antibody-coated tube kit. The kit shows less than 0.2% cross-reactivity with codeine and morphine-glucuronide. Unconjugated morphine concentrations were confirmed by gas chromatography/mass spectrometry (GC/MS) using deuterated morphine as the internal standard. The blood was precipitated with 10% trichloroacetic acid (TCA) and concentrated hydrochloric acid (HCl), centrifuged, and decanted. The supernatant was then either diluted (unhydrolyzed) or heated to 100 degrees C, 30 min (hydrolyzed), followed by a wash with 4:1 chloroform:isopropranol. The upper aqueous layer was then saturated with sodium bicarbonate (NaHCO3) and extracted with 4:1 chloroform:isopropranol. The organic layer was evaporated, derivatized with trifluoroacetic anhydride (TFA), and analyzed by selected ion monitoring (SIM) GC/MS. Comparison of the results for unconjugated morphine by radioimmunoassay and unhydrolyzed morphine by GC/MS gave a correlation coefficient of r = 0.98, n = 100. Unconjugated morphine ranged from 0 to 100% of total morphine with a mean of 42%, n = 200, for heroin or morphine involved deaths. Review of 56 putative rapid deaths gave a mean of 68% unconjugated morphine with a range of 26 to 100%. The ratio of unconjugated to total morphine was found to be stable in postmortem blood after more than a year of storage at room temperature, within the precision of the method.     

Postmortem Concentration and Redistribution of Diazepam,Methadone, and Morphine with Subclavian and Femoral Vein Dissection/Clamping

Postmortem redistribution (PMR) concerns blood drug concentration variations after death, depending on many factors such as sampling site and technique. In our study, we focused on sampling method. 30 cases were sampled, each at cardiac, subclavian, femoral, and popliteal sites. Targeted substances were diazepam, methadone, and morphine. Blind stick and dissection/clamping techniques were concomitantly performed at subclavian and femoral sites. Subclavian and femoral concentrations were compared according to technique used. To assess the influence of sampling technique on PMR, central/peripheral ratios were calculated depending on sampling method. Results show that drug concentrations tend to be lower when drawn from a clamped subclavian or femoral vein whereas ratios including subclavian and/or femoral blood concentration are influenced according to the technique used. In conclusion, clamping a subclavian or femoral vessel before sampling tends to result in lower drug concentrations and may influence ratios, suggesting the importance of isolating vessels from thoraco‐abdominal viscera.     

Partition coefficient, blood to plasma ratio, protein binding and short-term stability of 11-nor-Delta(9)-carboxy tetrahydrocannabinol glucuronide

11-Nor-Delta(9)-carboxy tetrahydrocannabinol glucuronide (THCCOOglu) is a major metabolite of tetrahydrocannabinol in blood. Despite its mass spectrometric identification already in 1980, further physicochemical data of THCCOOglu have not been established. Therefore, the octanol/buffer partition coefficient P and the blood to plasma ratio b/p for THCCOOglu concentrations of 100 and 500ng/ml were investigated. Protein binding of the glucuronide was established from spiked albumin solutions at a level of 250ng/ml as well as from authentic samples. The data were compared to those of 11-nor-Delta(9)-carboxy tetrahydrocannabinol (THCCOOH). In addition, the short-term stability of THCCOOglu in plasma at different storage temperatures was studied. Analysis was performed by LC/MS/MS. The glucuronide partition coefficient P (mean: 17.4 and 18.0 for 100 and 500ng/ml, respectively) was unexpectedly lipophilic at pH 7.4. Its blood to plasma ratios averaged 0.62 and 0.68 at 100 and 500ng/ml, respectively. THCCOOglu was highly reversibly bound to albumin (mean: 97%), and the mean fraction bound did not differ from that determined from authentic samples. THCCOOglu degraded even at a storage temperature of 4 degrees C and THCCOOH was identified as a major decomposition product.     

Fatal Oral Methylphenidate Intoxication with Postmortem Concentrations

Methylphenidate (MPD) is a widely prescribed stimulant used primarily for the treatment for attention‐deficit/hyperactivity disorder (ADHD). Suicide attempts involving MPD ingestion have been well described; however, deaths attributed solely to MPD ingestion have not been reported. A 62‐year‐old woman was found dead on her floor. The only discrepancy in among her medication quantities was that >three hundred 10 mg MPD tablets were missing. Analysis utilizing gas chromatography–mass spectrometry revealed elevated postmortem MPD peripheral and central blood, liver and vitreous humor concentrations. Considering both the central blood to peripheral blood ratio (0.89) and the liver to peripheral blood ratio (3.3), MPD does not appear subject to significant postmortem redistribution. With no other identifiable cause of death, we report what appears to be the first isolated MPD ingestion associated with a fatality.     

The extent of postmortem drug redistribution in a rat model.

The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbamazepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemazine) or chloroquine was administered together with nortriptyline orally to rats 90 min prior to sacrifice. Heart blood was sampled immediately before sacrifice and after 2 h postmortem, as it has previously been shown that this is sufficient time for postmortem concentration changes to occur in heart blood. Blood was also sampled from the clamped abdominal inferior vena cava (representing peripheral blood) and tissue samples were taken from lungs, myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor together with a specimen from the minced carcass. Drugs were analyzed by high performance liquid or gas chromatography. For phenobarbital, acetaminophen and carbamazepine the postmortem to antemortem blood drug concentration ratios were close to 1.0 and tissue concentrations were low. The postmortem to antemortem heart blood drug concentration ratio for chloroquine (6.9 +/- 1.5) was higher than for nortriptyline (3.5 +/- 0.3), and the remaining drugs (codeine, verapamil, amphetamine, mianserin, and trimeprazine) showed ratios of the same magnitude as nortriptyline. The postmortem to antemortem blood drug concentration ratios for both heart blood and blood from the vena cava and also the lung to antemortem blood drug concentration ratio were closely related to the apparent volume of distribution for the drugs studied (p < 0.001). Accordingly, an apparent volume of distribution of more than 3-4 L/kg is a good predictor that a drug is liable to undergo postmortem redistribution with significant increments in blood levels. The postmortem drug concentration in blood from vena cava was closely related to the antemortem blood level, confirming that among the postmortem samples, the peripheral blood sample was the most representative for the antemortem blood concentration.     

Evaluation of post-mortem ethanol concentrations in pericardial fluid and bone marrow aspirate

This study confirmed post-mortem ethanol concentrations in pericardial fluid and bone marrow aspirate in comparison with those in the blood in medicolegal autopsy cases (n = 140, within 48 h post-mortem). The specimens were examined by head-space gas chromatography/mass spectrometry. Ethanol concentrations in the pericardial fluid (y) were approximately equivalent to those in peripheral blood (x): y = 0.99x + 0.02, n = 44, r = 0.972. A high stomach ethanol concentration (>10 mg/ml) appeared to mildly affect the pericardial levels. There was no significant interference in drowning cases. Ethanol concentrations in bone marrow aspirates (y) also showed a good correlation with those in the peripheral blood (x): y = 0.77 x + 0.02, n = 20, r = 0.981. A dissociation was observed in cases of delayed death from hemorrhagic/traumatic shock and elderly victims. These findings suggest that pericardial fluid and bone marrow aspirate can be used as an alternative material when adequate blood specimens are not available.     

Analysis of biofluids for flunitrazepam and metabolites by electrospray liquid chromatography/mass spectrometry

A rapid and sensitive liquid chromatography/electrospray ionization mass spectrometry (LC/MS) procedure has been developed for the analysis of biofluids containing flunitrazepam and its metabolites. Specimens were spiked with deuterated analogs of the analytes. Urine specimens were enzymatically hydrolyzed and blood specimens were untreated. Extractions were carried out using CleanScreen DAU SPE cartridges. The drugs were separated on a C18 column using a methanol-water-ammonium hydroxide (60:40: 0.03 v/v) mobile phase. After determination of base peaks using full scan mass spectrometry, the mass spectrometry method was optimized to operate in selected-ion monitoring (SIM) mode for the base peak of each analyte. Positive findings were confirmed by LC/MS/MS using the same mobile phase and column. This analytical procedure allows for the detection of low levels of flunitrazepam and metabolites in biofluids. It is useful for ascertaining the role of flunitrazepam in cases of drug-facilitated sexual assault.     

Simultaneous screening and quantitation of 18 antihistamine drugs in blood by liquid chromatography ionspray tandem mass spectrometry

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is presented for the simultaneous screening and quantitation of 18 antihistamine drugs in blood samples. Sample pretreatment involved liquid-liquid extraction of the basic antihistamines followed by a second extraction of the acidic antihistamines. The recoveries were 43-113% for basic drugs and 23-66% for acidic drugs. The combined extracts were run by LC on C(18) reversed phase column using acetonitrile-ammonium acetate mobile phase at pH 3.2. The mass spectrometric analysis was performed with a triple stage quadrupole mass analyzer. Screening was performed using multiple reaction monitoring (MRM) and any compounds tentatively identified as antihistamine drugs were then automatedly verified by their Product Ion Spectra in a subsequent MS/MS run.Quantitation was based on the MRM data from the screening step. In validation tests, the method showed good linearity at the relevant concentrations. The attained limits of quantitation varied between 0.0005 and 0.01mg/l in blood and were lower than the therapeutic concentrations (C(max)). The limits for identification by Product Ion Spectra were also lower than C(max), except for clemastine, which has exceptionally low concentrations in blood. The intra-assay relative standard deviations were better than 10% and the inaccuracy varied between 39% for levocabastine and 5% for cyclizine, the majority of the values being <20%.     

Determination of Nicotine,Cotinine and Trans‐3′‐Hydroxycotinine using LC/MS/MS in Forensic Samples of a Nicotine Fatal Case by Oral Ingestion of e‐cigarette Liquid,

Nicotine is a potent neurotoxin alkaloid and is used in e‐cigarette liquid. The LC/MS/MS method was linear over 0.01–1.0 mg/L (r² = 0.992–0.995). Limit of detection and limit of quantitation were 0.001 mg/L (S/N = 3) and 0.003 (S/N = 10). The inaccuracy and imprecision were <13.2%. The recoveries were >99.3%. A 39‐year‐old dentist was found dead lying on the floor under the couch in his dental clinic. The concentration of nicotine, cotinine, and trans‐3′‐hydroxycotinine (heart blood/peripheral blood) was analyzed as follows: 87.2/85.2 mg/L (ratio 1.0), 1.4/1.1 mg/L (ratio 1.3), and 0.012/0.0089 mg/L (ratio 1.3), respectively. The concentration of nicotine was determined to be 6734.8 mg/kg in gastric contents and 7262.0 mg/L in remaining e‐liquid. Only, high concentration of nicotine was detected in the gastric contents as well as the two pieces of evidence collected from the death scene. This fatal case resulted from oral ingestion of e‐cigarette liquid. It is estimated that at least 714 mg of nicotine was orally ingested.     

Brain concentrations of cocaine and benzoylecgonine in fatal cases

Since cocaine in blood rapidly hydrolyzes to benzoylecgonine, cocaine concentrations determined in postmortem blood may not reflect the presence or concentration of cocaine in the body at the time of death. The interpretative value of the determination of cocaine and benzoylecgonine in brain tissue was investigated. Cocaine and benzoylecgonine were quantitated by coextraction and formation of the propyl derivative of benzoylecgonine followed by selected ion monitoring gas chromatography/mass spectrometry (GC/MS) using electron ion impact ionization. Cocaine and benzoylecgonine were found to be evenly distributed throughout the brain. Cocaine and benzoylecgonine concentrations were stable in frozen brain tissue (-4 degrees C) on reanalysis after 1 to 3 months of storage, and in refrigerated tissue (10 degrees C) after 30 days of storage. Blood, brain, and liver concentrations of cocaine and benzoylecgonine in 37 cocaine overdose cases and 46 cases in which cocaine was incidental to the cause of death were reviewed. The ratios of cocaine/benzoylecgonine in the toxic cases (brain mean 14.7 and blood mean 0.64) were clearly different from those found in the incidental cases (brain mean 0.87 and blood mean 0.27). The brain/blood ratios of cocaine and benzoylecgonine concentrations generally were characteristic of the time elapsed since cocaine dosing. In cocaine overdose cases, the mean ratio was 9.6 for cocaine and 0.36 for benzoylecgonine. These are within the range found in animal studies for brain/blood ratios of cocaine and benzoylecgonine 0.5 to 2 h after cocaine administration. In incidental cases, the brain/blood ratios were mean 2.5 for cocaine and 1.4 for benzoylecgonine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Morbidity Involving the Hallucinogenic Designer Amines MDA and 2C‐I*

Abstract: A case is presented of a 39‐year‐old woman who suffered severe debilitation because of a hemorrhagic stroke in the context of substance abuse. The patient presented to the emergency room with rapidly diminishing mental status, hypertension, and vasoconstriction; her friends provided a history of ingestion of cocaine, 3,4‐methylenedioxymethamphetamine (MDMA), and 2C‐I, a novel designer amine. A multi‐targeted LC‐MS/MS method for sympathomimetic amines and related drugs in urine detected and quantified 2C‐I and MDA, while ruling out MDMA. The cause of the stroke was determined to be an underlying cerebrovascular abnormality called Moyamoya, secondary to substance abuse. In clinical laboratories, gas chromatography–mass spectrometry or liquid chromatography–tandem mass spectrometry (LC‐MS/MS) confirmation of a positive amphetamine immunoassay is usually directed only towards amphetamine, methamphetamine, MDMA and MDA. This report demonstrates the utility of testing for a wider menu of compounds using LC‐MS/MS in order to better characterize the prevalence and toxicities of novel amines such as 2C‐I.     

A fatal dichlorvos poisoning: concentrations in biological specimens

Abstract:  A 54-year-old man was found dead with a bottle containing a brownish fluid near him. A toxicological screening was carried out in blood, urine, and stomach content. Only dichlorvos (2,2 dichlorovinyl O-O dimethylphosphate or DDVP) was found. A simple and rapid method, using DDVP-D₆ as an internal standard, was developed for the determination of DDVP by gas chromatography/mass spectrometry (GC/MS). The method was linear from 1 to 10 mg/L. Intraday and interday precisions were all <15%. DDVP concentration in cardiac blood was approximately four times higher than in peripheral blood. A high concentration was found in the heart showing a cardiac tropism of DDVP, kidney and lung concentrations being much lower. No DDVP was found in liver. DDVP stomach content was 38 g. The amount presumed ingested was 82 g, c . 1000 mg/kg of body. The oral LD₅₀ for DDVP ranges between 20 and 1090 mg/kg in animals but is not known for humans.     

LC-MS/MS法快速测定全血中25种精神药物的研究

目的建立人全血中25种精神药物快速测定的LC-MS/MS方法,并应用于分析杭州地区药物影响下驾驶(driving under the inference of drugs,DUID)情况。方法以乙腈沉淀蛋白,离心后取上清液,氮气流下吹干,残渣以初始流动相复溶,离心后取上清分析;采用C18色谱柱(50mm×3.0mm,2.6μm)分离,流动相:0.1%甲酸水(A相),乙腈:甲醇=1:1(B相),梯度洗脱;质谱检测,采用串联质谱电喷雾离子源,正电离扫描,多反应监测(MRM)。结果 25种精神药物在0.05~20ng/m L范围内线性良好,R=0.994 4~0.999 6;定量下限为0.05ng/m L;提取回收率为83.0%~99.7%;方法回收率为80.2%~97.4%;日内精密度(RSD)为1.6%~14%;日间精密度(RSD)为3.1%~14%。以该法测定杭州市公安司法鉴定中心留存的全血样品3140例,25种精神药物至少一种的检出率为3.7%。结论本方法灵敏、快捷、准确,适用于全血中25种精神药物快速检测。     

A new marker for estimation of bloodstain age by high performance liquid chromatography.

The applicability of a new marker for estimation of bloodstain age by reverse-phase high performance liquid chromatography (HPLC) is described. Using a microBondasphere C18 column with a two step linear gradient of 10.5-46.25% acetonitrile in 0.1% trifluoroacetic acid, an intriguing peak (unidentified) at a retention time of about 5 min was observed on chromatograms from human adult bloodstains and designated as 'X'. The area of this peak, which could be detected in extracts of bloodstains, but not in their fresh whole blood, increased with time. The ratios of the X area to heme area in bloodstains stored at room temperature and 4 degrees C for up to 52 weeks old linearly correlated with stain age by plotting on a double logarithmic scale. In bloodstains exposed to fluorescent light at room temperature, the regression equation calculated from the ratios (Rx) and the ages of stains in weeks (W) is ln(1000.Rx) = 1.1084 + 0.3937.ln(7.W), and the coefficient of correlation (r) is 0.9776 (n = 144, P < 0.001). When stains were stored at 37 degrees C, the ratio transformed into logarithms correlated linearly with stain age. The regression equation describing the relationship in bloodstains exposed to fluorescent light at 37 degrees C is ln(1000.Rx) = 2.4477 + 0.0866.W (r = 0.9826, n = 144, P < 0.001). The results of the present study suggest that the HPLC method may be applicable to the estimation of bloodstain age.     

Hair analysis of seven bodybuilders for anabolic steroids,ephedrine, and clenbuterol

Several bodybuilders, all winners of international competitions, were arrested for trafficking of a number of doping agents including anabolic steroids, ephedrine, beta-adrenergics, human chorionic gonadotropin, antidepressants, and diuretics. In accordance with the recent French law against doping, the judge asked to test seven bodybuilders to identify doping practices. Hair and urine specimens were collected for analysis. After decontamination, a 100 mg hair strand was pulverized in a ball mill, hydrolyzed, extracted, and derivatized to be tested by GC/MS for anabolic steroids, beta-adrenergic compounds, ephedrine, and other doping agents. Urine was analyzed for anabolic steroids and metabolites, beta-adrenergic compounds, ephedrine, and human chorionic gonadotropin, in addition to a broad spectrum screening with GC/MS. The following compounds were detected in urine: ephedrine (29 and 36 ng/mL, n = 2), clenbuterol (0.2 to 0.3 ng/mL, n = 3), norandrosterone (4.7 to 100.7 ng/mL, n = 7), norethiocholanolone (0.9 to 161.8 ng/mL, n = 6), stanozolol (1 to 25.8 ng/mL, n = 4), methenolone (2.5 to 29.7 ng/mL, n = 4), testosterone (3 to 59.6 ng/mL, n = 7), epitestosterone (1 to 20.4 ng/mL, n = 7) and ratio testosterone/epitestosterone >6 for four subjects (18.5 to 59.6). The following drugs were detected in hair: ephedrine (0.67 and 10.70 ng/mg, n = 2), salbutamol (15 to 31 pg/mg, n = 3), clenbuterol (15 to 122 pg/mg, n = 6), nandrolone (1 to 7.5 pg/mg, n = 3), stanozolol (2 to 84 pg/mg, n = 4), methenolone (17 and 34 ng/ml, n = 2), testosterone enanthate (0.6 to 18.8 ng/mg, n = 5), and testosterone cypionate (3.3 to 4.8 ng/mg, n = 2). These results document the doping practice and demonstrate repetitive exposure to anabolic compounds and confirm the value of hair analysis as a complement to urinalysis in the control of doping practice.     

Postmortem determination of the biological distribution of sufentanil and midazolam after an acute intoxication

A case is presented of a death caused by self-injection of sufentanil and midazolam. Biological fluids and tissues were analyzed for midazolam by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS) and for sufentanil by GC/MS. Midazolam was extracted from basified fluids or tissues homogenated with n-butyl chloride and analyzed by HPLC by using a phosphate buffer: acetonitrile (60:40) mobile phase on a mu-Bondapak C18 column at 240 nm. Sufentanil was extracted from basified fluids and tissue homogenates with hexane:ethanol (19:1). GC/MS methodology for both compounds consisted of chromatographic separation on a 15-m by 0.25-mm inside diameter (ID) DB-5 (1.0-micron-thick film) bonded phase fused silica capillary column with helium carrier (29 cm/s) splitless injection at 260 degrees C; column 200 degrees C (0.8 min) 10 degrees C/min to 270 degrees C; and electron ionization and multiple ion detection for midazolam (m/z 310), methaqualone (IS, m/z 235), sufentanil (m/z 289), and fentanyl (IS, m/z 245). Sufentanil concentrations were: blood 1.1 ng/mL, urine 1.3 ng/mL, vitreous humor 1.2 ng/mL, liver 1.75 ng/g, and kidney 5.5 ng/g. Midazolam concentrations were: blood 50 ng/mL, urine 300 ng/mL, liver 930 ng/g, and kidney 290 ng/g. Cause of death was attributed to an acute sufentanil/midazolam intoxication and manner of death a suicide.     

甲基苯丙胺对大鼠外周血中肾上腺素、去甲肾上腺素及肿瘤坏死因子-α的影响

目的观察甲基苯丙胺（MA）长时间给药对大鼠外周血中肾上腺素（N）、去甲肾上腺素（NE）及肿瘤坏死因子-α（TNF-α）的影响。方法雄性SD大鼠25只随机分成实验组（20只）和对照组（5只）,实验组再分为1、2、4、8周给药组（每组5只）。采用MA（10mg/kg）进行腹膜下注射制作染毒模型,应用放射免疫酶标技术检测大鼠外周血中N和NE;应用酶联免疫吸附试验（ELISA）检测外周血中TNF-α的水平。结果实验组各大鼠饮食量下降及饮水量增加,其外周血中N和NE水平增高,TNF-α表达增强,与对照组比较均有显著性差异（P〈0.05）。结论长时间使用MA可以引起外周血中N和NE增高及TNF-α表达增强,可能是MA引起心脏损害的重要机制之一。