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A rapid, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been developed and validated for the simultaneous analysis of hydrocodone (HYC) and its metabolite hydromorphone (HYM) in human plasma. A robotic liquid handler and a 96-channel liquid handling workstation were used to aliquot samples, to add internal standard (I.S.), and to extract analytes of interest. A 96-well mixed-mode solid-phase cartridge plate was used to extract the analytes and I.S. The chromatographic separation was on a silica column (50 x 3 mm, 5-microm) with a mobile phase consisting of acetonitrile, water and trifluoroacetic acid (TFA) (92:8:0.01, v/v). The run time for each injection was 2.5 min with the retention times of approximately 2.1 and 2.2 min for HYC and HYM, respectively. The tandem mass spectrometric detection was by monitoring singly charged precursor-->product ion transition 300-->199 (m/z) for HYC, and 28-->185 (m/z) for HYM. The validated calibration curve range was 0.100-100 ng/ml, based on a plasma volume of 0.3 ml. The correlation coefficients were greater than or equal to 0.9996 for both HYC and HYM. The low limit of quantitation (LLOQ) was 0.100 ng/ml for both HYC and HYM with signal-to-noise ratio (S/N) of 50 and 10. respectively. The deuterated analytes, used as internal standards, were monitored at mass transitions 303-->199 (m/z) for HYC-d3 and 289-->185 (m/z) for HYM-d3. The inter-day (n= 17) precision of the quality control (QC) samples were < or = 3.5% RSD (relative standard deviation) for HYC and < or = 4.7% RSD for HYM, respectively. The inter-day accuracy of the QC samples were < or = 2.1% RE (relative error) for HYC and < or = 1.8% RE for HYM. The intra-day (n=6) precision and accuracy of the QC samples were < or = 2.6% RSD and < or = 3.0% RE for HYC, and < or = 4.7% RSD and < or = 2.4% RE for HYM. There was no significant deviation from the nominal values after a 5-fold dilution of high concentration QC samples by blank matrix. The QC samples were stable when kept at room temperature for 24-h or experienced three freeze-thaw cycles. The extraction recoveries were 86% for HYC and 78% for HYM. No detectable carryover was observed when a blank sample was injected immediately after a 2500 ng/ml sample that was 25-fold more concentrated than the upper limit of quantitation (ULOQ).  相似文献   
2.
摘要 目的:研究罗哌卡因联合氢吗啡酮硬膜外自控镇痛在妊娠期糖尿病患者剖宫产术中的应用效果。方法:选择2018年1月~2019年6月我院行剖宫产术的81例妊娠期糖尿病患者,将其随机分为两组。对照组采用常规肌内注射镇痛的方式进行干预,当产妇无法忍受疼痛时肌内注射哌替啶100 mg。观察组在剖宫产术结束后连接自控镇痛泵,使用氢吗啡酮 0.3 mg+0.75 %罗哌卡因20 mL。比较两组干预前后的醛固酮(aldosterone,ALD)、皮质醇(cortisol,Cor)、血管紧张素Ⅱ(Angiotensin-Ⅱ,Ang-Ⅱ)、去甲肾上腺素(noradrenaline,NE)、血管活性肠肽(vasoactive intestinal peptide,VIP)、胃动素(motilin,MTL)、胆囊收缩(cholecystokinin,CCK)和胃泌素(gastrin,GAS)、血清单核细胞趋化因子蛋白(monocyte chemokine protein-1,MCP-1)、白介素-6(interleukin-6,IL-6)、高迁移率族蛋白(high mobility group protein,HMGB-1)水平的变化。结果:干预后,两组的VLD、Cor、Ang-Ⅱ和NE均较治疗前明显升高(P<0.05),且观察组干预后1 d、2 d的VLD、Cor、Ang-Ⅱ和NE明显低于对照组(P<0.05);干预后,两组的VIP和CCK均较治疗前明显升高(P<0.05),MTL和GAS均较治疗前明显降低(P<0.05),且观察组干预后1 d、2 d的VIP和CCK明显低于对照组(P<0.05),MTL和GAS明显高于对照组(P<0.05);干预2 d后,两组的血清MCP-1、IL-6和HMGB-1水平均较治疗前明显降低(P<0.05),且观察组的血清MCP-1、IL-6和HMGB-1水平明显低于对照组(P<0.05)。结论:罗哌卡因联合氢吗啡酮硬膜外自控镇痛能改善妊娠期糖尿病患者剖宫产术后的胃肠功能,抑制全身炎症反应。  相似文献   
3.
目的:比较吗啡与氢吗啡酮在小儿静脉自控镇痛(PCIA)应用中的镇痛效果及副作用。方法:选取40名6~10岁择期行下肢骨科手术的患儿,术毕即予PCIA,随机分为两组:M组(吗啡背景剂量15μg/kg/h,PCA剂量15μg/kg)和H组(氢吗啡酮背景剂量3μg/kg/h,PCA剂量3μg/kg),每组20例。记录患儿PCIA后3、6、12、24和48h的FLACC疼痛评分、Ramsay镇静评分、PCA次数及不良反应的发生情况(恶心呕吐、皮肤瘙痒、尿潴留、过度镇静、呼吸抑制)。结果:两组患儿各时间点FLACC疼痛评分、Ramsay镇静评分比较均无统计学差异(P均0.05)。术后第二天,M组PCA次数少于H组,差异存在统计学意义(P0.05)。M组皮肤瘙痒发生率(15%)显著高于H组(0%)(P0.05),两组其余不良反应的发生情况比较均无统计学差异(P均0.05)。结论:氢吗啡酮与吗啡用于小儿术后PCIA的镇痛效果和安全性相当。  相似文献   
4.
High-performance liquid chromatographic assays for the O- and N-demethylated oxidative metabolites of hydrocodone and oxycodone formed in human liver microsomes are described. A solvent-solvent extraction/re-extraction procedure followed by reversed-phase HPLC with UV detection at 210 nm allows for the quantification of hydromorphone, norhydrocodone, oxymorphone and noroxycodone. Calibration curve concentration ranges were 0.63-400 microM (0.18-114 microg/ml) and 1.25-400 microM (0.36-114 microg/ml) for hydromorphone and norhydrocodone, respectively and 0.13-20 microM (0.04-6.03 microg/ml) and 1-200 microM (0.30-60 microg/ml) for oxymorphone and noroxycodone, respectively. Assay performance was determined by intra- and inter-assay precision and inaccuracies for quality control samples and was <15% for all metabolites at each quality control concentration. These methods provide good precision, accuracy and sensitivity for use in in vitro kinetic studies investigating the oxidative metabolism of hydrocodone and oxycodone in human liver microsomes.  相似文献   
5.
目的:探讨氢吗啡酮术后镇痛对直肠癌患者Dixon术后肠功能恢复的影响。方法:选择直肠癌行Dixon术的患者36例,随机分为氢吗啡酮组(H组)和吗啡组(M组),每组18人。两组患者均行静脉自控术后镇痛,其中H组镇痛药物采用氢吗啡酮+昂丹司琼,而MS组则采用吗啡+昂丹司琼。术后常规医疗处理。结果:两组患者在年龄、性别、文化程度无统计学差异(P0.05)。两组患者术后VAS评分及HR、MAP变化均没有统计学差异(P0.05)。与M组相比,H组患者术后不良反应的发生率明显降低(P0.05),肠鸣音恢复时间、术后第一次排气时间和第一次排便时间均明显缩短(P0.05)。结论:相对于吗啡,氢吗啡酮用于术后镇痛更有利于直肠癌患者术后肠功能的恢复,并减少术后不良反应的发生率。  相似文献   
6.
摘要 目的:对麻醉诱导使用右美托咪啶和氢吗啡酮对比格犬术中痛阈和麻醉维持用药量进行比较研究。方法:实验分四组:低剂量右美托嘧啶组(low-dose dexamethymine,LDD)、高剂量右美托咪定(high-dose dexamethymine,HDD)、低剂量氢吗啡酮组(low-dose hydromorphone,LHD)、高剂量氢吗啡酮组(high-dose hydromorphone,HHD),采用对诱导麻醉手术期间的比格犬测定其热痛阈和电痛阈数值,抽取四组比格犬的静脉血,采用酶联免疫吸附法(ELISA)测定血清中疼痛介质和炎症因子的含量,前列腺素E2(prostaglandin E2,PGE2)、P物质(substance P,SP)、β-内啡肽(β-endorphin,β-EP),白介素-6(interleukin 6,IL-6)、单核细胞趋化因子蛋白(monocyte chemotactic factor protein,MCP-1)、高迁移率族蛋白(high mobility group protein,HMGB-1),对麻醉诱导手术期间各组比格犬的心率(Heart rate,HR)、舒张压(diastolic blood pressure,DBP)、平均值(mean blood pressure,MBP)和收缩压(systolic blood pressure,SBP)进行监测;记录手术持续时间(从最初切口到最后缝合的放置的时间),麻醉持续时间和拔管时间。结果:高剂量右美托咪定(HDD)和高剂量氢吗啡酮组(HHD)可以降低麻醉诱导手术期间比格犬的热痛阈和电痛阈值,血清中疼痛介质和炎症因子的含量的测量结果显示高剂量麻醉诱导会降低相关因子介质的含量,相对于低剂量诱导比格犬的HR、舒张压(DBP)、平均值(MBP)和收缩压(SBP)值增加。结论:对麻醉诱导使用高剂量的右美托咪啶和氢吗啡酮会降低比格犬术中痛阈和延长麻醉维持时间。  相似文献   
7.
Zheng M  McErlane KM  Ong MC 《Life sciences》2004,75(26):3129-3146
The main objective of this paper is to report the identification and synthesis of norhydromorphone, a novel metabolite of hydromorphone, and its antinociceptive activities when tested in the formalin test as compared to other known analgesics. In addition, we are reporting for the first time the lack of antinociceptive activities of hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide in the rat formalin test. Norhydromorphone was isolated and identified as a metabolite of hydromorphone in a cancer patient's urine. An authentic standard of norhydromorphone was synthesized. The identity of norhydromorphone in the urine sample was confirmed by comparing the LC retention time and MS ion fragmentation with the synthetic standard using a liquid chromatographic-mass spectrometric-mass spectrometric (LC-MS-MS) assay. Norhydromorphone was found to be a minor metabolite of hydromorphone in the urine. Additionally, the antinociceptive activities of norhydromorphone, hydromorphone, morphine, dihydromorphine, dihydroisomorphine, hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide were determined in the rat formalin test following intraperitoneal (i.p.) administration. Only limited antinociception was observed and no significant increase in antinociception was detected at the three doses tested. The increased polarity of norhydromorphone as compared to hydromorphone due to the primary piperidine nitrogen may make it less favorable to cross the blood-brain-barrier (BBB), which may be partly responsible. In addition, lower intrinsic antinociceptive activity, which remains to be determined, could also contribute to the low antinociception. Our results also show that hydromorphone was five times as potent as morphine in the formalin test, while dihydromorphine and dihydroisomorphine were equipotent to and 36% as potent as morphine, respectively. Hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide did not exhibit any antinociceptive effect at the doses tested. The results further underscore the importance of a free C3-OH to the analgesic effect of morphine alkaloids.  相似文献   
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