Simultaneous stereoselective analysis of venlafaxine and O-desmethylvenlafaxine enantiomers in clinical samples by capillary electrophoresis using charged cyclodextrins

Capillary electrophoresis (CE) was used for the simultaneous chiral determination of venlafaxine (Vx), a new antidepressant drug and its main active metabolite. O-desmethyl venlafaxine (ODV). Among the charged cyclodextrins (CD) tested, phosphated gamma-CD was the most appropriate. Resolution of Vx and ODV was obtained with 50 mM phosphate buffer (pH 2.5) containing 20 mg/ml of phosphated gamma-CD. After optimisation of the method (including robustness), validation was carried out. Vx and ODV concentrations, as well as the enantiomeric ratio, were investigated in clinical samples. Chiral determination of Vx and ODV was performed after a simple liquid-liquid extraction (LLE). In the tested concentration range (25-500 ng/ml), coefficients of correlation were superior to 0.996. Within-day and between-day accuracy and precision were determined at three different concentrations for each enantiomer. Analyses of clinical samples (n = 16) exhibited non-racemic ratios for Vx and ODV, which suggests a stereoselective metabolism in humans

Assessment of the uptake of neonatal and young infant referrals by community health workers to public health facilities in an urban informal settlement, KwaZulu-Natal, South Africa.

BACKGROUND: Globally, 40% of the 7.6 million deaths of children under five every year occur in the neonatal period (first 28 days after birth). Increased and earlier recognition of illness facilitated by community health workers (CHWs), coupled with effective referral systems can result in better child health outcomes. This model has not been tested in a peri-urban poor setting in Africa, or in a high HIV context. METHODS: The Good Start Saving Newborn Lives (SNL) study (ISRCTN41046462) conducted in Umlazi, KwaZulu-Natal, was a community randomized trial to assess the effect of an integrated home visit package delivered to mothers by CHWs during pregnancy and post-delivery on uptake of PMTCT interventions and appropriate newborn care practices. CHWs were trained to refer babies with illnesses or identified danger signs. The aim of this sub-study was to assess the effectiveness of this referral system by describing CHW referral completion rates as well as mothers' health-care seeking practices. Interviews were conducted using a structured questionnaire with all mothers whose babies had been referred by a CHW since the start of the SNL trial. Descriptive analysis was conducted to describe referral completion and health seeking behaviour of mothers. RESULTS: Of the 2423 women enrolled in the SNL study, 148 sick infants were referred between June 2008 and June 2010. 62% of referrals occurred during the first 4 weeks of life and 22% between birth and 2 weeks of age. Almost all mothers (95%) completed the referral as advised by CHWs. Difficulty breathing, rash and redness/discharge around the cord accounted for the highest number of referrals (26%, 19% and 17% respectively). Only16% of health workers gave written feedback on the outcome of the referral to the referring CHW. CONCLUSIONS: We found high compliance with CHW referral of sick babies in an urban South African township. This suggests that CHWs can play a significant role, within community outreach teams, to improve newborn health and reduce child mortality. This supports the current primary health care re-engineering process being undertaken by the South African National Department of Health which involves the establishment of family health worker teams including CHWs. TRIAL REGISTRATION NUMBER: ISRCTN41046462

Determination of risperidone in human plasma by HPLC-MS/MS and its application to a pharmacokinetic study in Chinese volunteers

This study presents a rapid, specific and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of risperidone (RIS) in human serum using paroxetine as an internal standard (IS). An Alltima-C18 column (2.1 mm×100 mm, 3 μm) and a mobile phase consisting of 0.1% formic acid-acetonitrile (40:60, v/v) were used for separation. The analysis was performed by selected reaction monitoring (SRM) method, and the peak area of the m/z 411.3→191.1 transition for RIS was measured versus that of the m/z 330.1→192.1 transition for IS to generate the standard curves. The assay linearity of RIS was confirmed over the range 0.25~50.00 ng/ml and the limit of quantitation was 0.05 ng/ml. The linear range corresponds well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations were 1.85%~9.09% and 1.56%~4.38%, respectively. The recovery of RIS from serum was in the range of 70.20%~84.50%. The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test versus reference products) in 18 healthy male Chinese volunteers. The result suggests that two formulations are bioequivalent