A decade of HPLC-MS/MS in the routine clinical laboratory--goals for further developments

During the past decade, tandem mass spectrometry hyphenated to liquid chromatography separation systems (HPLC-MS/MS) has developed to an important technology in clinical chemistry — not only for research purposes but also for routine use. At present, most important application fields are target analyses in therapeutic drug monitoring (TDM) and metabolic disorders diagnosis. The essential strengths of HPLC-MS/MS include potentially high analytical specificity, wide range of applicability to small and large molecules, capability of multi- and mega-parametric tests, and the opportunity to develop powerful assays with a high degree of flexibility within a short time frame. The technique has overcome important limitations of GC-MS and is characterized by short analytical runtimes, applicability to thermo labile, polar and large molecules, and straightforward sample preparation. However, implementation of HPLC-MS/MS assays still requires substantial expertise and know-how. At the present, its application is limited to a rather small number of clinical routine laboratories. Nonetheless, HPLC-MS/MS has the potential to be further developed to a commonly applied high-throughput technique in clinical chemistry, complementary to present standard techniques as photometry and ligand binding methods. This review intends to characterize working characteristics of present day HPLC-MS/MS instrumentations used in clinical routine laboratories. Limitations of currently available systems and applications will be critically discussed. Required instrument improvements supporting the successful spreading of HPLC-MS/MS in laboratory medicine within the next decade will be outlined.     

Topiramate Overdose: Clinical and Laboratory Features

Limited data exist on overdose with new antiepileptic drugs. We reviewed the medical records of two patients who took a topiramate overdose as a suicide attempt. We recorded their medical and seizure histories, concomitant antiepileptic medications, neurologic examination, and laboratory findings at the time of presentation following the overdose. We also recorded their progress and the evolution of laboratory abnormalities. Both patients progressed to coma and had generalized convulsive status epilepticus, requiring intubation and treatment with benzodiazepines. Both patients recovered within 2 days but had a non-anion-gap metabolic acidosis that persisted for 5-6 days. Physicians should carefully monitor patients treated with topiramate who develop signs of clinical depression. The non-anion-gap metabolic acidosis observed may be due to inhibition of renal cortical carbonic anhydrase.     

Treatment of US Crotalidae Bites

In the US, two antivenins are marketed for the treatment of snake envenomation. The horse-derived serum-globulin-based Antivenin (Crotalidae) Polyvalent (ACP) has been available since 1954. There are few data on the efficacy and incidence of adverse events that occur following the administration of ACP. Most of the data are retrospective, anecdotal, or case reports. In 2000, ovine-derived serum-globulin-based ACP (Crofab®) became available. Crofab® is said to cause fewer reactions than ACP, but there are few comparative data to substantiate this claim. Although both antivenins ameliorate the systemic symptoms following snake envenomation, the efficacy of either antivenin in decreasing oedema and swelling is unknown for a number of reasons. Clinical trials are small and have not included control arms. The degree of oedema, as well as the efficacy of the antivenin in decreasing oedema, may depend on the genera of the snake (usually unknown) that envenomated the patient. This article compares available data on clinical aspects of the two antivenins. More prospective data are needed to determine the comparative efficacy of the two antivenins, or the efficacy of Crofab® in preventing tissue oedema. There are still unanswered questions regarding the optimal dosing regimen of Crofab®.     

小红参的化学成分研究

小红参的化学成分研究徐晓莹，周金云，方起程（中国医学科学院中国协和医科大学药物研究所，北京１０００５０）小红参（Ｒｕｂｉａｙｕｎｎａｎｅｎｓｉｓ（Ｆｒａｎｃｈ）Ｄｉｅｌｓ）是茜草科茜草属植物云南茜草的根（１）。民间根据小红参有温经通络、活血祛风、软坚...     

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海南粗榧新碱衍生物HH07A对体外L1210细胞的杀伤作用

体外培养的小鼠L1210细胞被HH07A2μg·ml^-1作用24h后,与对照组细胞相比,其细胞数不再增长,有丝分裂数及集落形成率下降,细胞形态及细胞周期动力学均发生一定的变化。且HH07A大剂量短期作用抑制Ll210细胞集落形成的效率高于低剂量持续作用。     

高效液相色谱流通池法测定紫草中假紫草素的含量

高效液相色谱法测定紫草提取物中的假紫草素时,出现20个峰,需时75min,主峰保留时间55min,常规方法制备工作曲线很费时。本文报道一种新的工作曲线法——流通池法的原理和方法,测定结果与常规方法一致,可以节省时间。