Quantification of piritramide in human colostrum.

WHAT IS KNOWN AND OBJECTIVE: In our university hospital (UZBrussel), one of the options to control post-operative pain after a Caesarean section under general anaesthesia is to administer piritramide by patient-controlled intravenous analgesia (PCIA). As no information is available about the possible transfer of this synthetic narcotic analgesic into breastmilk, women are frequently advised not to breastfeed their newborn. A sensitive liquid chromatographic (LC) method coupled with UV detection will therefore be developed and validated for the quantification of piritramide in colostrum samples to evaluate the presence of the analgesic in the first milk. METHODS: The method included the isolation and concentration of piritramide from colostrum using protein precipitation and solid-phase extraction (SPE) using a mixed-mode cation exchange sorbent. Subsequently, the extracted samples were analysed on a microbore C18 column (1 mm id) and a mobile phase consisting of 15 mm ammonium hydroxide in methanol/tetrahydrofuran/water 50 : 10 : 40 V/V/V. RESULTS AND DISCUSSION: As colostrum contains a high amount of proteins, mixed-mode cation exchange SPE was preceded by a 1 : 2 dilution and protein precipitation with phosphoric acid followed by double centrifugation of the samples. The reversed-phase LC-UV method used a mobile phase at alkaline pH to obtain a selective method for piritramide and the internal standard pipamperone. After investigating the validation characteristics (linearity, accuracy, precision and stability), samples from ten patients who had received piritramide via PCIA during the first 48 h post-partum were analysed. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first method described for the quantification of the synthetic narcotic analgesic piritramide in colostrum samples. The obtained results suggest that after the administration of this opioid by PCIA to nursing mothers low concentrations of piritramide can be found in the first milk, but are mostly below the limit of quantification of 30 ng/mL.

Dysfunctional astrocytic regulation of glutamate transmission in a rat model of depression.

Depression is usually associated with alterations in the monoaminergic system. However, new evidences suggest the involvement of the glutamatergic system in the aetiology of depression. Here we explored the glutamatergic system in a rat model of depression (i.e., the flinders sensitive line (FSL)) to reveal the mechanism underlying the emotional and cognitive aspects associated with the disease. We showed a dramatically elevated level of baseline glutamatergic synaptic transmission by whole-cell recordings as well as impairment in long-term potentiation induced by high-frequency stimulation in hippocampal slices from FSL rats compared with Sprague-Dawley rats. At behavioural level, FSL rats displayed recognition memory impairment in the novel object recognition test. Enantioselective chromatography analysis revealed lower levels of D-serine in the hippocampus of FSL rats and both synaptic plasticity and memory impairments were restored by administration of D-serine. We also observed dysfunctional astrocytic glutamate regulation including downregulation of the glia glutamate transporter GLAST as shown by western blot. One possibility is that the dysfunctional astrocytic glutamate reuptake triggers a succession of events, including the reduction of D-serine production as a safety mechanism to avoid NMDA receptor overactivation, which in turn causes the synaptic plasticity and memory impairments observed. These findings open up new brain targets for the development of more potent and efficient antidepressant drugs.

Development and evaluation of a linear regression method for the prediction of maximal chiral separation of basic drug racemates by cyclodextrin-mediated capillary zone electrophoresis.

An important step in method development of chiral separations with neutral cyclodextrins (CDs) as chiral selectors is the estimation of the CD concentration that gives the highest degree of separation. From the equation [S]opt=1/(K1K2)(1/2) this optimal CD concentration can be calculated if any knowledge is available about the binding constants K1 and K2 of both enantiomer complexes. These values can be obtained by measuring the effective velocities of each enantiomer as a function of the selector concentration and fitting these profiles by non-linear least-square regression. An alternative approach has been developed which makes it possible to predict the optimal CD concentration from a few experiments performed at low CD concentrations. The model is developed using some antimycotic imidazole derivatives (econazole, miconazole and isoconazole) as test substances and hydroxypropyl-beta-CD as chiral selector. The results obtained by this method are in good agreement with those from non-linear least-square regression.