Preliminary investigation of the application of on-line membrane extraction of trifluoroacetic acid as an aid to improvement of negative ion electrospray mass spectrometry data.

We have recently investigated the biodegradation of a number of acidic aromatic compounds that give excellent chromatography using trifluoroacetic acid (TFA) based HPLC methods. Unfortunately HPLC methods using TFA are not usually compatible with detection by negative ion mass spectrometry as TFA suppresses ionisation of the analyte during the electrospray process. We present a preliminary investigation of the use of an anion-exchange micro-membrane suppressor to remove TFA on-line post column with the aim of improvement of mass spectral data using an aromatic acid as an example, Thus LC-MS using a TFA based HPLC method with negative ion mass spectral detection is shown to be possible with good sensitivity.

Diagnosis of pulmonary embolism by use of urinary TNF alpha and its soluble TNF receptor I.

The purpose of this clinical study was to determine the concentration of soluble tumor necrosis factor in urine of patients with pulmonary embolism (PE), verses voluntary control individuals. Sixteen patients (ages 24 to 74 years) with diagnosis of PE, documented by ventilation perfusion scan or pulmonary angiogram, were the subjects of this study. Ten cc of urine was obtained from each patient and subjected to a solid-phase enzyme-linked immunosorbent assay thus determining the soluble tumor necrosis factor (TNF) receptor I (R I) and TNF alpha levels in these samples. In this pilot study of PE cases, a statistically significant elevation in urinary levels of TNF alpha and soluble TNF R I was demonstrated in PE patients. The average urinary soluble TNF R I in normal subjects was 1,029 pg/mL and in PE patients the average TNF R I was 3,734.4 pg/mL. The clinical diagnosis of PE is a challenging problem for the physician. Late diagnosis and delayed management of this condition could be associated with massive PE. Although pulmonary angiography is the gold standard for diagnosis of PE, it requires expensive equipment, trained radiologists, and the patient could be at risk of sensitivity to contrast agents.

Cerebrospinal fluid penetration of cefpirome in patients with non-inflamed meninges.

Twenty patients (mean age 52 +/- 12 years, mean weight 75 +/- 15 kg) scheduled for elective myelogram or spinal anaesthesia were enrolled to determine the cerebrospinal fluid (CSF) penetration of a new expanded spectrum cephalosporin antibiotic, cefpirome (HR-810). A single 2 g intravenous dose of cefpirome was administered as a bolus between 1 and 8 h before lumbar puncture. Blood samples were collected at 15 pre-determined times and a single CSF sample was obtained at the time of lumbar puncture. Serum and CSF cefpirome concentrations were determined by high performance liquid chromatography. The mean maximal serum concentration of cefpirome was 264 +/- 76 mg/L. A mean steady-state volume of distribution of 20 +/- 4 L, clearance of 7.4 +/- 1.3 L/h, and half-life of 2.5 +/- 0.5 h were determined. Mean CSF concentrations were 0.50 +/- 0.11 mg/L at 1-2 h post dose (n = 4), 0.57 +/- 0.13 mg/L at 2-4 h post dose (n = 4), 0.76 +/- 0.34 mg/L at 4-6 h post dose (n = 7), and 0.83 +/- 0.29 mg/L at 6-8.3 h post dose (n = 5). Blood:brain barrier permeability to cefpirome may not be a limiting factor as CSF concentrations were rapidly attained. Further studies are required to determine the mechanism of cefpirome transport between plasma and CSF.