血液和脑脊液中利多卡因的气相色谱-质谱检测研究

目的建立血液和脑脊液中利多卡因的气相色谱-质谱联用定性、定量检测方法。方法血液或脑脊液盐酸酸化后,氢氧化钠碱化(pH=9),乙醚提取,氮气流下挥干,乙醇定容,气相色谱-质谱联用仪分析,选择离子监测模式检测(86,58,72,87),定性、定量检测血液和脑脊液中利多卡因。结果血液和脑脊液中利多卡因的线性范围为1.0～60.0μg·mL-1(r=0.9999),检出限为0.02μg·mL-1(S/N=3),加样回收率为85%～103%,麻醉致死犬血液和脑脊液中检出利多卡因,结果满意。结论该法选择性好,干扰少,灵敏,准确,可用于生物体液中利多卡因的定性和定量检测。     

甲醛处理后人脊髓中的利多卡因和布比卡因的同时测定

目的建立经甲醛防腐处理后人脊髓中利多卡因和布比卡因同时定量测定的HPLC分析法,以满足法医学鉴定的需要。方法以空白人脊髓经甲醛防腐处理后添加标准利多卡因和布比卡因,对样品的前处理方法及仪器测试条件、方法的线性范围、检测限、精密度、回收率进行系统考察。结果所建方法中两药物的线性范围为0.5～10.0ug.g-1(利多卡因r=0.9999;Bupivacaine r=0.9998),检测限利多卡因为15ng布比卡因为20ng,日内、日间分析的相对标准偏差均在4.3％以内,加样回收率在97.3％～100.3％之间。结论经甲醛防腐处理后的脊髓可同时进行利多卡因和布比卡因定量测定。所建方法准确、实用,适用于法医学鉴定及相关研究。     

高效液相色谱法检测人脊髓中的利多卡因

建立高效液相色谱法对人脊髓中利多卡因进行分析的方法 ,以扩大药 (毒 )物检测范围及检测手段 ,适应法医学鉴定及对特殊检材检验的需要。用利多卡因标准品及空白脊髓标准添加实验 ,对色谱条件、样品处理方法、回收率及方法的线性和精密度进行了系统考察。所建方法线性范围是2 0～20 0μg/ml(r=0 9999) ,最低检测限为0 2μg/ml(S/N≥3),加样回收率为82 4 %～92 7% ,该法选择性好、不受干扰。所建方法灵敏、准确、简捷 ,可用于法医学鉴定。     

人脑脊液中利多卡因的高效液相色谱分析

目的 建立人脑脊液中利多卡因的高效液相色谱(HPLC)分析方法。方法 以空白人脑脊液添加标准利多卡因进行HPLC分析,并系统考察实验中的色谱条件、样品处理方法、线性关系、精密度及回收率。结果 所建方法的线性范围是1.0～20.0μg·ml-1(r=0.9993),最低检测浓度为1.0μg·ml-1(S/N≥3),日内、日间检测的相对标准偏差≤3.0％,回收率为98.3％～102.7％。结论 所建方法定量检测人脑脊液中的利多卡,灵敏、准确、快速。     

Tissue distribution of lidocaine in critical care patients after intubation

We investigated tissue distribution of lidocaine in 33 patients after endotracheal intubation with Xylocaine jelly that contains 2% lidocaine hydrochloride. Blood levels of monoethylglycinexylidide (MEGX), an active metabolite of lidocaine, were also determined. Five patients (Group A) were alive on arrival and six patients (Group B) resumed heartbeats after cardiopulmonary resuscitation (CPR). The survival times for Groups A and B ranged from 3 to 72 h. The remaining 22 patients (Group C) did not survive cardiopulmonary arrest on arrival (CPAOA). Systemic distribution of lidocaine was measured in nine patients from Group C. The liver-to-kidney lidocaine ratios and cerebrum-to-cerebrospinal fluid lidocaine ratios were: Group A, 0.1-0.7 and 1.4-3.6, respectively; Group B, 0.2-0.8 and 1.2-2.3, respectively; Group C, 0.1-17 and 0.2-1.0, respectively. MEGX was detected in all blood samples from Group A and only two samples from Group B. No MEGX was detected in samples from Group C. Our results indicate that the absorption of tracheal lidocaine during natural circulation results in a cerebrum-to-cerebrospinal fluid lidocaine ratio of 1.2 or more, whereas absorption during artificial circulation by cardiac massage gives a ratio of 1.0 or less. The cerebrum-to-cerebrospinal fluid lidocaine ratio may be a more useful index to estimate circulatory dynamics of patients during CPR than the liver-to-kidney lidocaine ratio. MEGX was not a useful parameter for monitoring circulatory changes during cardiac massage.     

Determining the state of the deceased during cardiopulmonary resuscitation from tissue distribution patterns of intubation-related lidocaine

The objective of this study was to determine whether the concentrations of lidocaine, used for endotracheal intubation, in body fluids and tissues reflect the state of the circulation of the deceased during cardiopulmonary resuscitation. The tissue distribution of lidocaine was investigated in seven individuals (Cases 1-7) who underwent medical treatment with endotracheal intubation using Xylocaine jelly (a 2% lidocaine hydrochloride preparation), before being pronounced dead. Six patients (Cases 1-6) had cardiopulmonary arrest on arrival at hospital. In Cases 1-4, there was no restoration of heartbeat during cardiopulmonary resuscitation. However, systemic distribution of intubation-related lidocaine was observed and the kidney-to-liver ratios of lidocaine were less than 1. In Cases 5 and 6, the heartbeat resumed temporarily with cardiac massage, and a kidney-to-liver lidocaine ratio greater than 1 was observed. In Case 7, where the patient was comatose upon admission to hospital, the kidney-to-liver ratio of lidocaine was also greater than 1. These phenomena were substantiated in animal experiments. Our results indicate that the absorption of tracheal lidocaine during the artificial circulation resulting from cardiopulmonary resuscitation results in a kidney to liver ratio of less than 1, whereas absorption during natural circulation gives a ratio greater than 1. The kidney-to-liver ratio of intubation-related lidocaine may give useful information on the state of a patient during cardiopulmonary resuscitation.     

利多卡因在蛛网膜下腔麻醉致死犬体内的分布

目的 观察利多卡因蛛网膜下腔致死犬体内的分布及脊髓液、脊髓与血液中利多卡因含量的比值。方法薄层扫描法检测血、脊髓液、侧脑室液、各节段脊髓和各脏器组织中利多卡因含量。结果 蛛网膜下腔麻醉致死犬脊髓液、各节段脊髓、脑、血液和其它各脏器中利多卡因含量分别为485.6±51.5μg/ml、226.8±35.2-353.8±44.0μg/g、44.9±11.51μg/g、40.3±6.5μg/ml和13.5±13.7-38.0±9.8μg/g。脊髓液与血液中利多卡因含量之比为12.4±2.7,各节段脊髓与血液之比为5.7±0.9-9.0±2.6。结论 蛛网膜下腔麻醉致死犬脊髓液中利多卡因含量最高,脊髓中次之,血液和其它组织中含量较低。脊髓液/血液、脊髓/血液比值平均可达12.4和5.7-9.0。     

利多卡因硬膜外麻醉和静脉注射致死的动物模型

目的建立利多卡因硬膜外麻醉和静脉注射致死的动物模型。方法本地杂种犬18只其中6只经硬膜外腔、6只经股静脉注射利多卡因(63.35mg/kg体重),对照组3只经硬膜外腔、3只经股静脉按注射生理盐水(3.2ml/kg体重)。观察动物致死过程的生命体征变化及死后各组织器官的病理改变特点。结果硬膜外麻醉致死犬心电、血压和呼吸消失的平均时间分别为28 min(22~45 min)、23.6 min(20~42 min)、22 min(18~35 min);静脉注射致死犬血压、心电和呼吸消失的平均时间分别为6.5 min(5~8min)、8 min(6~10min)、7.2 min(4~9min);各器官病理改变均呈淤血、水肿等征象。结论该模型实验动物的表现和生命特征变化符合椎管内麻醉中毒、致死的表现,可用于利多卡因麻醉意外致死案件的法医学鉴定研究。     

Tissue distribution of intubation-related lidocaine in brain-dead patients

Tissue distribution of lidocaine that was used for endotracheal intubation during cardiopulmonary resuscitation (CPR) was measured in 3 patients who were brain-dead or near brain death. Case 1 was a 69-year-old female whose heartbeat was restored by CPR but stopped 10 hours later. The lidocaine ratios of cerebrum to blood (2.04) and diencephalon to blood (1.01) were within ranges of those found in non-brain-dead patients. Case 2 was a 77-year-old female whose heart resumed beating after CPR but stopped 66 hours later. The lidocaine ratios of cerebrum to blood (5.69), diencephalon to blood (18.7), and cerebellum to blood (11.3) were much higher than those in non-brain-dead patients. Case 3 was a 48-year-old male who had cardiopulmonary arrest following an acute subarachnoid hemorrhage. His heart resumed beating after resuscitation but ceased beating 114 hours after admission. Lidocaine was detected only from the cerebrum, cerebellum, and blood clots in the superior sagittal sinus at levels of 0.028, 0.024, and 0.007 mug/g, respectively. Tissue distribution of intubation-related lidocaine in brain-dead patients is useful as supplementary data for reviewing hemodynamic changes in their brains during medical treatment.     

利多卡因在蛛网膜下腔和静脉注射致死犬体内的死后分布

目的比较利多卡因在蛛网膜下腔和静脉注射致死犬体内的死后分布特点。方法犬12只,其中6只经蛛网膜下腔,另6只经股静脉匀速注入利多卡因(5×15mg/kg)致死,迅速解剖动物,取大脑、侧脑室脑脊液、腰段脊髓腔脑脊液、不同脊髓节段(颈髓、胸髓、腰髓、骶髓),心、肺、肝、脾、肾、胆汁、尿、心血、周围血、注射部位肌肉和注射部位20 cm以外肌肉等脏器组织和体液,用气质联用法定性,气相色谱法定量检测其中利多卡因含量。结果蛛网膜下腔注射致死犬体内利多卡因的含量由高到低顺序依次为腰段脊髓腔脑脊液、骶段脊髓、胸段脊髓、侧脑室脑脊液、腰段脊髓、颈段脊髓、肺、肾、注射部位肌肉、心、大脑、脾、心血、肝、周围血、胆汁、注射部位20 cm以外的肌肉、尿;静脉注射致死犬体内利多卡因的含量由高到低顺序依次为肾、心、肺、脾、大脑、肝、周围血、胆汁、心血、颈段脊髓、胸段脑脊液、注射部位肌肉、腰段脊髓、注射部位20 cm以外的肌肉、侧脑室脑脊液、尿、腰段脊髓腔脑脊液、骶段脊髓。结论蛛网膜下腔注射致死犬背侧脊髓液中利多卡因含量最高,静脉注射致死犬肾脏利多卡因含量最高,此分布特征可为利多卡因麻醉意外法医学鉴定中入体途径的判定提供参考。     

Concentrations of lidocaine and monoethylglycylxylidide (MEGX) in lidocaine associated deaths

Concentrations of lidocaine and MEGX were determined in a variety of tissues and other samples collected at autopsy. In 13 of the cases examined in which lidocaine was associated with death, tissue concentrations were greater than 15 mg/kg. Tissue concentrations in other patients treated with lidocaine were significantly lower.     

SPE-GC／MS检测生物样品中利多卡因、罗哌卡因、布比卡因

目的建立生物样品中利多卡因、罗哌卡因、布比卡因的固相萃取提取方法和气质检测方法。方法采用Oasis HLB固相萃取柱,以GC／MS定性定量。结果生物样品中利多卡因、罗哌卡因、布比卡因平均萃取回收率达74％以上,检测限0．01μg／mL,线性关系良好,相关系数R2=0．9900以上。结论方法操作简便快速,萃取回收率高,重现性好,可用于实际案件。     

A dextromoramide-related fatality

A 38-year-old man was found in his car suffering from a heart attack. Serum analysis by capillary gas chromatography and mass spectrometry confirmed the presence of dextromoramide (Palfium), methadone, and lidocaine. The serum concentrations at admission to the hospital were: 1.9 micrograms/mL of dextromoramide, 0.4 micrograms/mL of methadone, and 0.4 micrograms/mL of lidocaine. A serum alcohol analysis performed using headspace gas chromatography was negative.     

Tissue distribution of lidocaine after fatal accidental injection

The accidental death of a 64-year-old heart patient as a result of the injection of an incorrect dose of lidocaine is presented. The attending nurse inadvertently administered an intravenous bolus of 10 mL of 20% lidocaine (2g). The patient should have received 5 mL of 2% lidocaine (0.1 g). Such iatrogenic overdoses of lidocaine arise from confusion between prepackaged dosage forms. Lidocaine concentrations (mg/L or mg/kg were: blood, 30; brain, 135; heart, 106; kidney, 204; lung, 89; spleen, 115; skeletal muscle, 20; and adipose, 1.3. The results indicate that even during cardiopulmonary resuscitation as much as 38% of the administered dose of lidocaine may be found in poorly perfused tissue such as skeletal muscle and adipose.     

A case of homicide by lethal injection with lidocaine

This report describes a homicide by overdosage with lidocaine. The decedent, a 32-year-old male hospitalized for a lengthy period with acute intermittent porphyria and chronic pancreatitis, suffered apparent asystole and seizure. Failed resuscitation preceded death. A forensic autopsy was conducted based upon suspicions of alleged patient mistreatment by one of the attending nurses. Toxicological analyses revealed the presence of lidocaine in blood, liver, kidney, brain, and heart at 22.2 mg/L and 43.6, 28.3, 23.1, and 13.1 mg/kg, respectively. Also present were diazepam, phenytoin, and promethazine. Both diazepam and phenytoin had been administered during resuscitation, but lidocaine had not. The cause of death was determined to be ventricular arrhythmia precipitated by lidocaine overdosage. The administered dose was calculated to have been approximately 1500 mg. The manner of death was determined to be homicide. The nurse was arrested and subsequently tried for murder by administering a lethal quantity of lidocaine.     

红外光谱法用于安钠咖中咖啡因和苯甲酸钠快速定性和定量分析

目的建立安钠咖样品中咖啡因和苯甲酸钠快速定性和定量分析的红外光谱方法。方法采用高纯度咖啡因和苯甲酸钠混合制样的方法制备定性和定量建模样品,通过分析混合样品的红外光谱图,确定安钠咖样品中咖啡因和苯甲酸钠的特征吸收峰。采用偏最小二乘法(partial least squares,PLS)建立红外光谱定量模型。结果通过分析17个咖啡因和苯甲酸钠混合样品(咖啡因纯度范围10%~80%)的红外光谱图,确定了咖啡因的特征吸收峰为1698、1650、1237、972、743、609cm-1;苯甲酸钠的特征吸收峰为1596、1548、1406、845、708、679cm-1。将所有特征吸收峰均检出作为阳性判断依据时,48个安钠咖缴获样品中咖啡因和苯甲酸钠的阳性检出率均为100%。咖啡因PLS定量模型的线性范围为10%~80%,决定系数(R2)为99.9%,交叉验证均方差(root mean square error of cross validation,RMSECV)为0.68%,预测均方差(root mean square error of prediction,RMSEP)为0.91%;苯甲酸钠PLS定量模型的线性范围为20%~90%,R2为99.9%,RMSECV为0.91%,RMSEP为1.11%。配对样本t检验结果显示,高效液相色谱法和红外光谱法的测定结果差异无统计学意义。采用所建立的红外定量方法分析48个安钠咖缴获样品,咖啡因的纯度为27.6%~63.1%,苯甲酸钠的纯度为36.9%~72.3%。结论采用红外光谱法对安钠咖样品中的咖啡因和苯甲酸钠进行快速定性和定量分析,可提高检验鉴定效率、降低检验成本。     

Distribution of lidocaine and disopyramide in human blood and tissue, a case report of death caused by spinal anesthesia

An 11-year-old girl was anesthetized with hyper-baric solution of lidocaine as spinal anesthesia for an appendectomy in a surgical clinic. Respiratory arrest which occurred soon after the injection, was not discovered for a period of time. Since spontaneous respiration recovered within 2 h of intensive resuscitation, the patient was transferred to a community hospital for intensive care. Ten hours after the spinal anesthesia, she died of cardiac failure. The concentration of lidocaine in the brain was 5-10 times more than that in other tissues. The relationship between the possibility of malpractice of spinal anesthesia and tissue distribution of the drug was discussed. In addition to lidocaine, a toxic amount of disopyramide, an antiarrhythmic drug, was detected in the body. The distribution of disopyramide was also estimated, and the pharmacokinetics of disopyramide in plasma and tissues were studied experimentally in rats.     

Clarifying the complex chemistry of cobalt(II) thiocyanate-based tests for cocaine using single-crystal X-ray diffraction and spectroscopic techniques

Cobalt(II) thiocyanate-based tests are routinely used to screen cocaine products, with the formation of a blue species interpreted as a positive response. An array of other organic bases has been identified as false positives – including well-documented cocaine product adulterant lidocaine and its salt. False positives prompt continued test development, though improvements are hindered by unresolved product structures and reaction pathways. Toward greater clarity, cobalt(II) thiocyanate reactions with cocaine hydrochloride, along with lidocaine and its salt, were investigated using multiple analytical techniques. Reactions involving cocaine hydrochloride yielded glassy, amorphous blue material while reactions of lidocaine hydrochloride monohydrate produced larger, needle-like crystals whose structure was determined via single-crystal X-ray diffraction to be an ion pair (Hlidocaine⁺)₂([Co(SCN)₄]²⁻)·H₂O. While the blue precipitate isolated from reactions involving cocaine hydrochloride was unsuitable for crystallographic structure determination, comparative ultraviolet–visible, attenuated total reflectance infrared, and Raman spectroscopic analysis – along with elemental analysis – supports that this solid is comprised of a comparable ion pair (Hcocaine⁺)₂[Co(SCN)₄]²⁻. Pink crystals isolated from lidocaine reaction vessels were identified as coordination compounds cis-[CoL₂(SCN)₂] and trans-[CoL₂(SCN)₂] where L = lidocaine, while pink crystals from both cocaine hydrochloride and lidocaine hydrochloride monohydrate reaction vessels were the coordination polymer trans-[Co(H₂O)₂(SCN)₂]·H₂O. The results presented herein enable reaction optimization to favor a desired product, whether ion pair or coordination species.     

Impurity profiling of methamphetamine hydrochloride drugs seized in the Philippines

Methamphetamine hydrochloride is one of the most widely used illicit drugs in the Philippines. In this study, we describe the application of cluster analysis of trace impurities in the profiling of the seized methamphetamine drug samples. Thirty milligrams of a homogenized drug sample were dissolved in 1 mL of pH 10.5 buffer solution and extracted with ethyl acetate containing three internal standards. The trace impurities were identified using gas chromatography-mass spectrometry (GC-MS) and quantified by gas chromatography with a flame ionization detector (GC-FID). Following previously reported methodologies, 30 impurity peaks were selected from the GC-FID chromatograms. The peak areas and retention times were referenced to the internal standards. The peak areas of the selected peaks were then grouped for cluster analysis. In order to check for consistency of clustering, two further cluster analyses were performed using 40 and 50 impurity peaks. Changes in clustering were observed in going from 30 to 40 impurity peaks, while analyses using 40 and 50 impurity peaks gave similar results. Thus, for the seized drug samples used in this study, cluster analysis using at least 40 impurity peaks showed better consistency of clustering as compared to analysis using 30 peaks only. Ten of the impurity peaks were identified, of which four were identified for the first time in methamphetamine drug samples. These are p-bromotoluene, N-benzyl amphetamine, N-ethyl amphetamine, and N-ethyl methamphetamine. The presence of phenyl-2-propanone (P2P), N,N-dimethyl amphetamine, and N-formyl amphetamine is indicative that these casework samples were synthesized using the Leuckart method.     

Suicide due to oral ingestion of lidocaine: a case report and review of the literature

The Authors describe a rare case of suicide in a 31-year-old woman, due to oral ingestion of lidocaine; the histological and toxicological findings are discussed to provide useful information to the present experience with this particular modality of death. Histological examination revealed generalized stasis. In the myocardium we observed segmentation of the myocardial cells and/or widening of intercalated discs and associated group of hypercontracted myocardial cells with "square" nuclei in line with hyperdistended ones. Non-eosinophilic bands of hypercontracted sarcomeres alternating with stretched, often apparently separated sarcomeres, small foci of paradiscal contraction band necrosis, and perivascular fibrosis were observed too. Lidocaine was detected in the subject's urine through immunoenzymatic screening. Toxicological analysis by solid-liquid extraction and gas chromatography-mass spectrometry (GC-MS) analysis, was carried out to identify and quantify the individual substances present in the biological fluids and organs. Lidocaine concentrations were as follows: blood 31 microg/mL, gastric content 2.5 g, liver 10 microg/g, kidney 12 microg/g, brain 9 microg/g, spleen 24 microg/g, lung 84 microg/g, heart 9 microg/g, urine 9 microg/mL, and bile 6 microg/mL. No other drugs or alcohol were detected. When blood lidocaine reaches toxic levels, serious toxic symptoms associated with the central nervous system and cardiac system are noted. The overdose of lidocaine produces death from ventricular fibrillation or cardiac arrest. In this case, according to macroscopic and microscopic findings, the cause of death was most likely cardiac and possibly related to ventricular fibrillation.