Van Eeckhaut A, Vanfleteren P, Van Schoors J, Van Wanseele Y, Poelaert J, Michotte Y
Department of Pharmaceutical Chemistry and Drug Analysis, Center for Pharmaceutical Research (CePhar), Vrije Universiteit Brussel, Brussels, Belgium.
Department Anesthesiology and Perioperative Medicine, UZBrussel, Brussels, Belgium.
J Clin Pharm Ther. 2017 Jun;42(3):306-310. doi: 10.1111/jcpt.12515. Epub 2017 Mar 13.
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.
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 C column (1 mm id) and a mobile phase consisting of 15 mm ammonium hydroxide in methanol/tetrahydrofuran/water 50 : 10 : 40 V/V/V.
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.
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.
在我们的大学医院（布鲁塞尔大学医院），全身麻醉下剖宫产术后控制疼痛的一种选择是通过患者自控静脉镇痛（PCIA）给予匹利卡明。由于尚无关于这种合成麻醉性镇痛药可能转移至母乳中的信息，因此常建议女性不要母乳喂养新生儿。因此，将开发并验证一种灵敏的液相色谱（LC）方法并结合紫外检测，用于定量初乳样本中的匹利卡明，以评估初乳中是否存在该镇痛药。
该方法包括使用蛋白质沉淀法从初乳中分离和浓缩匹利卡明，并使用混合模式阳离子交换吸附剂进行固相萃取（SPE）。随后，将萃取的样本在微径C柱（内径1 mm）上进行分析，流动相由甲醇/四氢呋喃/水（50:10:40 V/V/V）中15 mM氢氧化铵组成。
由于初乳中含有大量蛋白质，在进行混合模式阳离子交换SPE之前，先将样品以1:2稀释，并用磷酸进行蛋白质沉淀，然后对样品进行两次离心。反相LC-UV方法使用碱性pH的流动相，以获得针对匹利卡明和内标匹泮哌隆的选择性方法。在研究了验证特性（线性、准确性、精密度和稳定性）后，分析了产后头48小时内通过PCIA接受匹利卡明的10名患者的样本。
据我们所知，这是首次描述的用于定量初乳样本中合成麻醉性镇痛药匹利卡明的方法。所得结果表明，在通过PCIA向哺乳期母亲给药这种阿片类药物后，初乳中可检测到低浓度的匹利卡明，但大多低于30 ng/mL的定量限。
