HPLC-ELSD法测定盐酸金刚烷胺颗粒中盐酸金刚烷胺的含量

目的:建立HPLC-ELSD法测定盐酸金刚烷胺颗粒中盐酸金刚烷胺的含量。方法:采用C18(4.6 mm×250 mm,5μm)色谱柱,流动相为乙腈-0.06%三氟乙酸溶液(20︰80),流速1.0 mL.min-1,柱温30℃,进样量10μL;检测器为ELSD,漂移管温度55℃,雾化气体为空气,载气流速为2.0 L.min-1。结果:盐酸金刚烷胺的线性浓度范围为80.48～281.68μg.mL-1(r=0.9991);平均回收率(n=9)为100.3%(RSD=0.9%)。结论:本方法较标准方法简便、可靠、准确,适合盐酸金刚烷胺颗粒的质量控制。     

Acute olanzapine overdose

Olanzapine, a thiobenzodiazepine derivate, is a recently released novel antipsychotic medication. The authors report the first case of overdose of olanzapine in an apparent suicide attempt. A 38‐year‐old schizophrenic patient was brought to a hospital emergency room following the ingestion of 12 10‐mg tablets of olanzapine. There were no serious clinical adverse effects. Copyright © 1999 John Wiley & Sons, Ltd.     

Acute myocarditis after massive phenelzine overdose

BACKGROUND: Monoamine oxidase inhibitors (MAOIs) are uncommonly used due to their high frequency of adverse effects, including tachycardia and hypertension. Recently, there has been renewed interest in the role of this class of drugs in treating a variety of psychiatric disorders. The clinical features of MAOI overdose are poorly characterised. This paper describes a novel cardiac complication of phenelzine toxicity in a previously healthy young adult with no history of cardiovascular disease. METHODS: A 23-year-old woman presented to hospital after massive phenelzine overdose, and the clinical features and pathological findings are discussed in light of existing literature. RESULTS: Clinical features of phenelzine toxicity included reduced consciousness level, seizures, and tachycardia, in keeping with previous reports. Unexpectedly, the patient developed severe and unexplained hypotension and impaired left ventricular function, and died 3 days after initial presentation. Post-mortem examination confirmed high serum phenelzine concentrations (4.1 mg/L) and histopathological features that were consistent with drug-induced acute myocarditis. CONCLUSION: Acute myocarditis was attributed to phenelzine in the absence of any plausible alternative explanation. This possible complication should be considered in patients who develop unexplained hypotension after phenelzine overdose.     

Status epilepticus after massive carbamazepine overdose

We report two patients who experienced status epilepticus after carbamazepine overdose. The first patient was an 18-year-old female with a history of epilepsy. She experienced 4 hour of persistent and prolonged seizures resistant to sodium amytal therapy. The status epilepticus ended with her death. The second patient was an 18-year-old male with a history of bipolar disorder. He experienced 5 hour of persistent and prolonged seizures that appeared to be resistant to diazepam, phenytoin, and phenobarbital. The seizures abated with the infusion of midazolam. This is a report of status epilepticus associated with wide complex tachycardia after carbamazepine overdose, which may be resistant to conventional therapy.     

Life-threatening bradyarrhythmia after massive azithromycin overdose

9-month-old infant was inadvertently administered azithromycin 50 mg/kg, taken from floor stock, instead of the prescribed ceftriaxone. Shortly thereafter, she became unresponsive and pulseless. The initial heart rhythm observed when cardiopulmonary resuscitation was started was a widecomplex bradycardia, with a prolonged rate-corrected QT interval and complete heart block. The baby was resuscitated with epinephrine and atropine, but she suffered severe anoxic encephalopathy. Torsade de pointes and QT-interval prolongation have been reported after administration of macrolide antibiotics, including azithromycin, both intravenously and orally. This has occurred especially in the context of coadministered drugs that inhibit the cytochrome P450 (CYP) 3A4 isoenzyme, such as ketoconazole and astemizole. However, bradycardia with complete heart block has not, to our knowledge, been reported specifically with intravenous administration of azithromycin alone, either with therapeutic doses or overdose. Clinicians should be alerted about the potential of azithromycin to cause life-threatening bradycardia, and pharmacy systems should be implemented to ensure special care in the safe administration of this drug, especially when dispensed from a point-of-care source.     

酸性染料比色法测定盐酸金刚烷胺糖浆的含量

本文采用溴甲酚绿的酸性染料比色法，于415nm波长处测定盐酸金刚烷胶糖浆的含量，平均回收率100．3％．RSD0．30％（n＝5）。方法简便，辅料无干扰。     

毛细管柱气相色谱法测定盐酸金刚烷胺有关物质

目的:建立气相色谱法测定盐酸金刚烷胺的有关物质并对有关物质进行确证。方法:采用毛细管柱,程序升温,FID检测器测定有关物质;采用MSD检测器,测得有关物质的EI质谱图,进行结构确证。结果:通过方法学验证,可以采用面积归一化法测定有关物质,检测限为2 ng;并确证了杂质A为二氨基取代金刚烷,杂质B为2-氨基金刚烷。结论:本方法准确、灵敏,可以控制盐酸金刚烷胺的质量。     

DNA damage in brain cells and behavioral deficits in mice after treatment with high doses of amantadine

Amantadine (AMA) is an uncompetitive antagonist of the N‐methyl‐d ‐aspartate receptor, with clinical application, acting on treatment of influenza A virus and Parkinson's disease. It has been proposed that AMA can indirectly modulate dopaminergic transmission. In high doses, the central nervous system is its primary site of toxicity. To examine deleterious effects on CNS induced by AMA, this study evaluated possible neurobehavioral alterations induced by AMA such as stereotyped behavior, the effects on locomotion and memory and its possible genotoxic/mutagenic activities. Adult male CF‐1 mice were treated with a systemic injection of AMA (15, 30 or 60 mg kg^?1) 20 min before behavioral tasks on open field and inhibitory avoidance. Higher AMA doses increased the latency to step‐down inhibitory avoidance test in the training session in the inhibitory avoidance task. At 60 mg kg^?1 AMA induced impairing effects on locomotion and exploration and hence impaired habituation to a novel environment. Stereotyped behavior after each administration in a 3‐day trial was observed, suggesting effects on dopaminergic system. Amantadine was not able to induce chromosomal mutagenesis or toxicity on bone marrow, as evaluated by the micronucleus assay. At the lowest dose tested, AMA did not induce DNA damage and it was unable to impair memory, locomotion, exploration or motivation in mice. However, higher AMA doses increased DNA damage in brain tissue, produced locomotor disturbances severe enough to preclude testing for learning and memory effects, and induced stereotypy, suggesting neurotoxicity.     

LC-MS/MS法测定人血浆中的金刚烷胺浓度及其药动学

目的建立HPLC-MS/MS分析方法测定人血浆中的金刚烷胺浓度,并用于研究健康受试者口服氨酚咖黄烷胺片后金刚烷胺的药动学。方法血浆经乙醚-二氯甲烷(4∶1,V/V)提取,采用C18柱为分析柱,甲醇-10 mmol.L-1醋酸铵溶液-冰醋酸(60∶40∶0.08,V/V/V)为流动相,流速1.0 mL.min-1,柱后分流,0.2 mL.min-1进入质谱,柱温35℃。质谱检测方式:多反应离子监测,选择监测的离子为m/z152→m/z135(金刚烷胺)和m/z275→m/z230(内标物,氯苯那敏)。结果金刚烷胺的线性范围为1~200μg.L-1(r=0.9999),血浆中金刚烷胺的最低定量限达1μg.L-1(RS,N>10),回收率>80%。结论本法简便、准确、灵敏度高,适用于金刚烷胺的药动学研究。     

单剂量口服复方氨酚烷胺胶囊在人体内的生物等效性

目的 选择18名受试者单剂量交叉po两种复方氨酚烷胺胶囊,评价其生物等效性.方法 用HPLC测定血中对乙酰氨基酚和咖啡因的药物浓度,用3p97软件计算药动学参数;用方差分析和双单侧t检验分析两种复方氨酚烷胺胶囊中对乙酰氨基酚和咖啡因的主要药动学参数.结果 对乙酰氨基酚的Tmax分别为0.99±0.47、0.88±0.39 h,Cmax分别为8.40±2.99、8.62±5.00 μg·ml-1,AUC0-24分别为35.42±9.54、33.84±10.37 mg·h·L-1;咖啡因的Tmax分别为0.94±0.24、0.90±0.19 h,Cmax分别为1.22±0.31、1.26±0.42 μg·ml-1,AUC0-24分别为8.80±2.01、8.43±2.23 mg·h·L-1.结论 两种制剂具有生物等效性.     

Brief overdose education can significantly increase accurate recognition of opioid overdose among heroin users

BackgroundIn an effort to increase effective intervention following opioid overdose, the New York State Department of Health (NYSDOH) has implemented programs where bystanders are given brief education in recognizing the signs of opioid overdose and how to provide intervention, including the use of naloxone. The current study sought to assess the ability of NYSDOH training to increase accurate identification of opioid and non-opioid overdose, and naloxone use among heroin users.MethodsEighty-four participants completed a test on overdose knowledge comprised of 16 putative overdose scenarios. Forty-four individuals completed the questionnaire immediately prior to and following standard overdose prevention training. A control group (n = 40), who opted out of training, completed the questionnaire just once.ResultsOverdose training significantly increased participants’ ability to accurately identify opioid overdose (p < 0.05), and scenarios where naloxone administration was indicated (p < 0.05). Training did not alter recognition of non-opioid overdose or non-overdose situations where naloxone should not be administered.ConclusionsThe data indicate that overdose prevention training improves participants’ knowledge of opioid overdose and naloxone use, but naloxone may be administered in some situations where it is not warranted. Training curriculum could be improved by teaching individuals to recognize symptoms of non-opioid drug over-intoxication.     

HPLC-ELSD法测定盐酸金刚烷胺片的溶出度

目的:采用HPLC-ELSD法建立盐酸金刚烷胺片溶出度的测定方法。方法:采用Agilent ZORBAX SB-C18(250 mm×4.6 mm,5μm)色谱柱,流动相为乙腈-0.06%三氟乙酸溶液(20∶80),流速1.0 mL.min-1,柱温为30℃;使用ELSD检测器,漂移管温度为55℃,雾化气体为空气,载气流量为1.8 L.min-1。结果:盐酸金刚烷胺浓度在39.56～197.8μg.mL-1范围内线性关系良好(r=0.9996);平均回收率(n=9)为99.9%。结论:本方法准确、可靠,灵敏度高,适用于盐酸金刚烷胺片溶出度的检测。     

Therapeutic drug monitoring in drug overdose

The treatment of poisoned patients is still largely defined by history, clinical assessment and interpretation of ancillary investigations. Measurement of drug concentrations is clinically important for relatively few compounds. Most measurements form an adjunct to and should not be considered a substitute for clinical assessment. Drug concentrations are particularly important for those compounds where the concentration is predictive of serious toxicity in an otherwise asymptomatic patient.     

金刚烷胺衍生物的设计、合成及其抗禽流感病毒活性

目的 设计合成金刚烷胺衍生物并对其进行抗禽流感病毒活性测试。方法 以金刚烷甲酰氯和氨基酸甲酯盐酸盐为起始原料经酰胺化、水解、成盐等反应依次得到3个系列金刚烷胺衍生物。以金刚烷胺为阳性对照,采用幼犬肾（MDCK）细胞系噬斑形成实验测定目标化合物的抗禽流感病毒活性。结果与结论 共合成了20 个未见报道的新化合物,目标化合物的结构均经¹H-NMR、IR、MS 谱确证;仅有化合物 A₅ 显示出较好的抗禽流感病毒活性。     

Therapeutic drug monitoring in drug overdose

The treatment of poisoned patients is still largely defined by history, clinical assessment and interpretation of ancillary investigations. Measurement of drug concentrations is clinically important for relatively few compounds. Most measurements form an adjunct to and should not be considered a substitute for clinical assessment. Drug concentrations are particularly important for those compounds where the concentration is predictive of serious toxicity in an otherwise asymptomatic patient.     

Fatality related to a 30-g venlafaxine overdose

A 30-g venlafaxine overdose resulted in death for a 39-year-old woman whose 43-day clinical course was highlighted by refractory hypotension and the resulting complications of bowel ischemia and perforation. Her venlafaxine and O-desmethylvenlafaxine levels, analyzed by high-performance liquid chromatography one day after ingestion, were 21.82 mg/L (therapeutic range 0.1-0.5 mg/L) and 3.33 mg/L (0.2-0.4 mg/L), respectively. These levels remained elevated for over 7 days. Postulated explanations for these extended elevated levels were saturation of drug metabolism, decreased drug metabolism, and existence of a genetic polymorphism. Our patient's venlafaxine overdose produced a wide variety of clinical challenges, to include seizures, tachycardia, decreased level of consciousness, refractory hypotension, and bowel dysmotility. In addition, this case augments the growing body of literature that suggests that venlafaxine may be fatal in overdose situations.