Development of a simple and sensitive HPLC-MS/MS method for determination of diazepam in human plasma and its application to a bioequivalence study

We developed a simple, sensitive, and effective ultra-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method with an electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) and positive ion modes to determine diazepam concentrations in human plasma using voriconazole as an internal standard (IS). Diazepam and IS were detected at transition 285.2→193.1 and 350.2→127.1, respectively. After liquid-liquid extraction (LLE) using 1.2 ml of ethyl acetate:n-hexane (80:20, v/v), diazepam and IS were eluted on a Phenomenex Cadenza CD-C18 column (150 × 3.0 mm, 3 µm) with an isocratic mobile phase (10 mM ammonium acetate in water:methanol [5:95, v/v]) at a flow rate of 0.4 mL/min. The peak retention time was 2.32 min for diazepam and 2.01 min for IS, respectively. The lower limit of quantitation (LLOQ) was 0.5 ng/mL (S/N > 10) using 50 µL of plasma, and no interferences were observed in chromatograms. Our analytical method was fully validated and successfully applied to a bioequivalence study of two formulations of diazepam in healthy Korean volunteers.

A case of transient cortical blindness following coronary angiography / 대한내과학회지

Transient cortical blindness is a known but rare complication occurring in 0.3~1% of patients undergoing cerebral or vertebral angiography. It is an extremely rare complication following cardiac catheterizaton and coronary arteriography. Cortical blindness is characterized by complete loss of visual perception and optokinetic nystagmus with preservation of ocular motility, pupillary responses, and normal fundoscopic examination. It has been suggested that its occurrence is due to an adverse reaction to the contrast agent, which causes an osmotic disruption of the blood-brain barrier. Patients outcome appears to be generally favorable with return of vision within 24-48 hr. We report a case of 48 year-old male patient with transient bilateral cortical blindness after coronary angiography.

Effects of Halothane, Fentanyl, and Propofol-Fentanyl Anesthesia on Functional Recovery of Stunned Myocardium in Dogs / 대한마취과학회지

BACKGROUND: Stunned myocardium may be mediated by intracellular Ca2+ overloading or oxygen derived-free radicals. Halothane and propofol have been shown to block Ca2+ channels. Propofol is also known to have antioxidant properties. The present study was aimed to investigate the effects of anesthetics on recovery of postischemic, reperfused myocardium in open-chest dogs. Incidence of ventricular arrhythmia upon ischemia and reperfusion was also determined. METHODS: Forty dogs were subjected to 15 min occlusion of left anterior descending coronary artery (LAD) followed by 3 hr reperfusion during halothane (n=10), fentanyl (n=12), or propofol plus fentanyl (n=11) anesthesia. Regional contractile function was assessed using percent systolic shortening (%SS), the preload recruitable stroke work slope (Mw), and peak systolic intramyocardial pressure (IMPs). Diastolic function was evaluated using time constant for isovolumic intramyocardial pressure decline of left ventricle (IMP-tau) and percent post-systolic shortening (%PSS). RESULTS: %SS in the halothane, fentanyl, and propofol-fentanyl groups was similar at 3 hours of reperfusion (58%, 60%, and 55% of baseline value, respectively). Moreover, Mw recovered to the baseline values in the early reperfusion period in all three groups. However, IMP-tau was significantly prolonged in the halothane group throughout the 3 hour reperfusion period, whereas it remained unchanged in the fentanyl and propofol-fentanyl groups. Coronary occlusion was associated with 9, 33, and 0% mortality rate due to ventricular fibrillation upon ischemia and reperfusion in the halothane, fentanyl, and propofol-fentanyl groups, respectively. CONCLUSION: These findings indicate that halothane, but not fentanyl and propofol- fentanyl, impairs myocardial relaxation, while recovery pattern of contractile function do not differ among three groups, and that halothane and propofol reduce reperfusion arrhythmia in the canine model of myocardial stunning.

Changes in Hemodynamics and Plasma Catecholamine Levels following Midazolam Premedication / 대한마취과학회지

The present study atternpted. to expiore the new benzodiazepine, midazolam, which is water-soluble, shorter-acting, more potent, and less irritating to inject than diazepam, and which has been used as premedication before induction of anesthesia in various elective surgeries. Forty patients (aged 20 to 50 and in ASA class I or II ) about to undergo simple elective surgery under general anesthesia entered the study. The patients were divided into the study group (n=20) that recieved 0.07 mg/Kg i.m midazolan premedication and the control group (n= 20) that recieved normal saline as sham premedication. The changes in the values of various hemodynamic parameters, i.e., heart rate and systolic, diastolic, mean arterial pressures, were monitored first before tracheal intubation, then at the time of intubation and 5, 10 and 30 minutes after intubation. The concentrations of plasma catecholamines i.e., epinephrine and norepinephrine, were measured before intubation and 5, 30 minutes after intubation. Systolic pressure and plasma epinephrine concentration before induction was significantly low in the study compared with the controls. At the time of intubation, sytolic, diastolic & mean arterial pressures were significantly low in the study group compared with the controls. Heart rates measured at 10 and 30 minutes postintubation were significantly low at 30 minutes postintubation in the study group compared with the controls as was plasma epinephrine levels at each instance of its measurement. In conclusion, midazolam-premedicated patients appear to maintain stable hemodynamies and plasma catecholamine levels. Our findings support that midazolam premedication effectively reduces stress response during induction period making it suitable induction for elective surgery.

A case of Holoprosencephaly

No abstract available.