Quantification of piritramide in human colostrum

Abstract

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.

Keywords: alkaline pH; colostrum; liquid chromatography; mixed-mode cation exchange; piritramide; solid-phase extraction.