Validation of rapid and simple LC-MS/MS method for determination of voriconazole in rat plasma.

A rapid, simple and sensitive LC-MS/MS analytical method was developed and validated for the determination of voriconazole (VRC) in rat plasma, using ketoconazole as internal standard (IS). Analysis was performed on a Shimadzu HPLC system using a Shimadzu C18 column and isocratic elution with acetonitrile-water-formic acid (60:40:0.05, v/v/v), at a flow of 1.0 mL/min (split ratio 1:5), and a mass spectrometer Micromass, equipped with a double quadrupole and an electrospray ionization interface, operated in a positive mode. Plasma samples were deproteinized with methanol (1:2) and 30 microL of the supernatant was injected into the system. The retention times of VRC and IS were approximately 3.3 and 2.7 min, respectively. Calibration curves in spiked plasma were linear over the concentration range of 50-2500 ng/mL with determination coefficient >0.98. The lower limit of quantification was 50 ng/mL. The accuracy of the method was within 5%. Intra- and inter-day relative standard deviations were less or equal to 12.5 and 7.7%, respectively. The applicability of the LC-MS-MS method for pharmacokinetic studies was tested using plasma samples obtained after intravenous administration of VRC to male Wistar rats. The reported method provided the necessary sensitivity, linearity, precision, accuracy, and specificity to allow the determination of VRC in pre-clinical pharmacokinetic studies.

Development and validation of a LC-MS/MS method with electrospray ionization for determination of LASSBio-579 in rat plasma.

A simple and sensitive LC-MS/MS analytical method was developed and validated for the determination of LASSBio-579 in plasma rat, using fluconazole as internal standard. Analyses were performed on a Shimadzu HPLC system using a Shimadzu C18 column and isocratic elution with acetonitrile-water (80:20, v/v), containing 0.4mM ammonium hydroxide and 0.2 mM acetic acid at a flow rate of 1.0 ml/min (split ratio 1:5). A Micromass triple quadrupole mass spectrometer, equipped with an electrospray ionization interface, operated in the positive mode. Plasma samples were deproteinized with acetonitrile (1:2) and 50 microl of the supernatant were injected into the system. The retention times of LASSBio-579 and IS were approximately 4.7 and 2.4 min, respectively. Calibration curves in spiked plasma were linear over the concentration range of 30-2000 ng/ml with determination coefficient >0.98. The lower limit of quantification was 30 ng/ml. The accuracy of method was within 15%. Intra- and inter-day relative standard deviations were less or equal to 13.5% and 6.4%, respectively. The applicability of the LC-MS/MS method for pharmacokinetic studies was tested using plasma samples obtained after intraperitoneal administration of LASSBio-579 to male Wistar rats. No interference from endogenous substances was observed, showing the specificity of the method developed. The reported method can provide the necessary sensitivity, linearity, precision, accuracy, and specificity to allow the determination of LASSBio-579 in pre-clinical pharmacokinetic studies.

Sinus node recovery after 25 years of atrial flutter.

This case report demonstrates that the sinus node can recover relatively quickly even after being suppressed by atrial flutter for 25 years, and that a permanent pacemaker may not always be necessary in all patients with sinus arrest after a successful atrial flutter ablation.

Therapeutic options in patients with reduced ejection fraction and nonsustained ventricular tachycardia.

The patient with a reduced ejection fraction and nonsustained ventricular tachycardia represents a common management problem for the physician. This article reviews the supporting evidence for the therapeutic options available for these patients according to the etiology of the reduced ejection fraction. In postinfarction patients, electrophysiology-guided implantable cardioverter defibrillator therapy improves survival more than antiarrhythmic therapy. In patients with nonischemic cardiomyopathy, the best therapy is yet undetermined. Ongoing clinical trials will hopefully direct future therapy.

Case report: is this SVT or VT? An exception to the rule.

This case illustrates the difficulties sometimes encountered by clinicians when using algorithms in diagnosing a wide-complex tachycardia based on a 12-lead EKG.

Histopathological correlation of ablation lesions guided by noncontact mapping in a patient with peripartum cardiomyopathy and ventricular tachycardia.

A patient with peripartum cardiomyopathy developed a nearly incessant nonsustained VT. Guided by a noncontact mapping system, the tachycardia was mapped to the mid-septum of the right ventricle and ablated. Despite transient success, the tachycardia recurred and the patient subsequently died of multiorgan failure. Histopathological correlation of the ablation site revealed a nontransmural lesion that may have contributed to the failure of the ablation.

Effect of varying atrial sensitivity, AV interval, and detection algorithm on automatic mode switching.

UNLABELLED: Automatic mode switching (AMS) is absolutely dependent on atrial tachyarrhythmia detection. The effects of programming several features that could influence tachyarrhythmia detection were assessed in 18 patients (six women; mean age 64 years) with pacemakers having AMS capability. The atrial electrogram amplitude in sinus rhythm at implant (SR-EGM), last measured atrial sensing threshold prior to tachycardia (A-SENS), and atrial sensing threshold for effective AMS during atrial tachyarrhythmia (AMS-SENS) were obtained. Additionally, ten patients had AV intervals increased from 60 to 200 ms, while seven patients had detection algorithms made more stringent from 5 beats at 150 beats/min to 11 beats at 200 beats/min to assess their effects on AMS efficacy. RESULTS: Sensitivities:Mean SR-EGM = 3.55 mV; mean A-SENS = 2.06 mV; and mean AMS-SENS = 1.46 mV. Fourteen patients developed atrial fibrillation and four atrial flutter. Thirteen of 14 patients who developed atrial fibrillation sensed adequately at > or = 1.0 mV in normal sinus rhythm (NSR), but only six patients had effective AMS at these settings in atrial fibrillation. Three of four patients who developed atrial flutter had effective AMS at > or = 2.0 mV. AV Interval:AMS was effective in eight of ten patients at AV intervals up to 200 ms. One patient lost AMS at an AV interval of 120 ms. Algorithm: In two of seven patients, AMS was not effective if the detection algorithm was more stringent than five beats at 150 beats/min. CONCLUSIONS: (1) In atrial fibrillation, effective AMS requires more sensitive atrial settings than in NSR; (2) AV intervals as short as 120 ms can interfere with AMS function; and (3) More stringent detection algorithms may be inappropriate for effective AMS function.

[Intracranial pressure. Direct measurement in the cisterna magna]. / Presión intracraneana. Medida directa en la gran cisterna.

The intracranial cisternal or supraoccipital punction in the sitting position, was undertaken in 523 cases, of which 329 presented increased intracranial pressure. The procedure must be done by experts, and was well tolerated. There were no cases of death, arterial hemorrhages or medullary lesions. In 451 cases CSF pressure was measured and CSF was extracted for laboratory examination. Pneumoencephalograms were undertaken with this method in 335 patients. The intracranial cisternal pressure in the sitting position is greater than the suboccipital or cervical cisternal pressure by 1.5 to 3cm H2O. Its value is practically equal to the pressure in the posterior fossa, and when the medial ventricular system is patent, is similar to the pressure in the supratentorial fossas. The intracranial cisternal punction has less risks than the suboccipital punction and can be undertaken in patients with rised intracranial pressure In 62 cases the tap was negative; this led to the diagnosis of amygdaline herniation and the procedure was interrupted without mishap. The authors consider that, in the future, the connection of the cisternal catheter with a transducer, will permit the continuous monitoring of the intracranial cisternal pressure.

Encephalography using supra-occipital tapping of the cisterna magna.

A report is given of the results of supra-occipital tapping of the cisterna magna and dynamic encephalography by that route. In 72 patients with cranial hypertension this encephalography was well tolerated. Supra-occipital tapping is less dangerous than suboccipital puncture as regards the possibility of injury to the medulla. In 38 cases, the method led immediately to the diagnosis of herniation of the tonsils.

Continuous peroperative supraoccipital cisternal drainage.

1. The technique of continuous peroperative supraoccipital cisternal drainage for intracranial decompression by means of a slow and progressive removal of CSF from the ventricles and the basal cisterns is described. 2. This procedure was used in eight patients with good results, considerable decompression being obtained with no untoward effects. 3. In four cases of intracranial aneurysm marked intracranial hypotension was obtained, greatly facilitating treatment of the lesions. 4. In four cases of brain tumour, the reduction of intracranial hypertension was not so great, and was complemented with general antihypertensive treatment. 5. Supraoccipital cisternal drainage removes intracranial CSF, but not the fluid in the spinal theca. The tonsils of the cerebellum are thus kept floating, and this, in our experience, has prevented them from impacting in the foramen magnum and compressing the medulla,

Intracranial circulatory insufficiency. Surgery of carotid atheroma.

Clinical and radiological studies are presented from 81 cases of intracranial circulatory insufficiency due to extracranial atherosclerosis, and the results of surgical treatment are given.