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.

Stability-indicating HPLC assays for the determination of piritramide and droperidol in PCA solution.

WHAT IS KNOWN AND OBJECTIVE: A mixture of morphine and droperidol is a well-established antiemetic for reducing the risk of postoperative nausea and vomiting. A mixture of piritramide and droperidol has not yet been evaluated in this context. Our objectives were to develop a high-performance liquid chromatographic assay for piritramide and droperidol in 0·9% saline, and to establish their stability under defined storage conditions. METHODS: The separation and assay of both drugs were attempted by high performance liquid chromatography (HPLC) using a RP-select B column and a mobile phase of 57:43% v/v methanol-monosodium phosphate solution 0·05 M at a flow rate of 1·2 mL/min. UV detection at 205 and 246 nm for piritramide and droperidol were used, respectively. RESULTS AND DISCUSSION: The HPLC method was successful. Linearity was shown for piritramide from 0·075 to 0·013 mg/mL and for droperidol from 0·8 to 0·2 mg/mL. The intra- and inter-day relative standard deviation (RSD, %) was 0·27% and 0·54% for piritramide and droperidol, respectively. The two drugs were stable for at least 72 h when stored under ambient light at room temperature. WHAT IS NEW AND CONCLUSION: Seventy-five milligrams piritramide and 2·5 mg droperidol diluted to 50 ml with 0·9% saline should be suitable for clinical use. At this dilution, a Dipidolor(®) and Xomolix(®), mixture, was stable when stored under ambient light exposure at room temperature for at least 72 h.

Stability of piritramide in patient-controlled analgesia (PCA) solutions.

For patient controlled analgesia, syringes with solutions of 1.5 mg/ml piritramide in 0.9% aqueous sodium chloride are used. The physical and chemical stability for dilutions of the commercially available preparation of piritramide is limited up to 72 hours by the manufacturer. Since application duration for patient-controlled analgesia can exceed that limited time, stability was investigated by HPLC. Our results show that these solutions are chemically stable over a time period of 60 days.