LC/MS/MS determination of omapatrilat, a sulfhydryl-containing vasopeptidase inhibitor, and its sulfhydryl- and thioether-containing metabolites in human plasma.

Omapatrilat, the most clinically advanced member of a new class of cardiovascular agents, vasopeptidase inhibitors, is under development at Bristol-Myers Squibb Pharmaceutical Research Institute for the treatment of hypertension and heart failure. An electrospray LC/MS/MS method has been developed and validated for the simultaneous determination of omapatrilat and its four metabolites in human plasma. Since omapatrilat and two of the metabolites are sulfhydryl-containing compounds, methyl acrylate was used to stabilize these compounds in human blood and plasma samples. Methyl acrylate reacted instantly with the sulfhydryl group to form a derivative that was stable in blood and plasma. Extraction of the analytes from plasma samples was achieved by semiautomated liquid-liquid extraction, where a robotic liquid handler performed the liquid-transferring steps. The mass spectrometer was operated in the negative ion selected-reaction-monitoring mode. The calibration curve ranges were 0.5-250 ng/mL for omapatrilat and one metabolite and 2.0-250 ng/mL for the other three metabolites.

Cervical cytology in a community laboratory.

A retrospective analysis of the results of 27,801 cervical smears from one year in a community laboratory was undertaken. This represented 23,820 individual patients. Abnormalities were seen in 9.3% of patients. Three point seven percent of patients had benign abnormalities, 5.5% had cervical intraepithelial neoplasia and 0.1% had major abnormalities. The incidence of cervical epithelial abnormality was highest in the 15-34 age group but major abnormalities were seen most often in the 55+ age group. Human papillomavirus was more commonly seen in the youngest age group. The presence of inflammation was reported in 65% of the smears. Thirty percent of smears had no endocervical cells and 0.6% were grossly inadequate. Fifteen percent of patients had repeat smears and 3% of total smears were judged unnecessary. Forty two point six percent of patients less than 55 years of age in the laboratory population base had a smear but only 7.9% of those over 55.

An audit of restricted antibiotic use in a general hospital.

An audit of the use of antibiotics restricted by the hospital formulary was undertaken by retrospective analysis of 73 written justifications for prescriptions provided to the pharmacy and the case notes. Half of the prescriptions were for therapeutic indications with the remainder divided almost equally between prophylactic and empirical use. The cost of therapy was $34,500. Antibiotic use was classified as appropriate or inappropriate. Inappropriate use was seen in 22 cases at an excess cost of $3828. Prophylactic use accounted for 13 of the inappropriate prescriptions, most frequently due to excessive duration of prescription. The use of amikacin where gentamicin was not contraindicated was seen in 4 of 9 inappropriate prescriptions. The infrequent use of the more expensive antibiotics and the potentially remediable inappropriate use seen with prophylaxis were gratifying aspects of this audit.