Nguyen Tam, Menten Laurien, Spriet Isabel, Quintens Charlotte, Van Schepdael Ann, Adams Erwin
Department of Pharmaceutical and Pharmacological Sciences, Pharmaceutical Analysis, KU Leuven, Leuven, Belgium.
Hospital Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.
Electrophoresis. 2022 May;43(9-10):970-977. doi: 10.1002/elps.202100275. Epub 2021 Nov 25.
Portable infusion pumps are an interesting solution to continue outpatient parenteral antimicrobial therapy (OPAT) at the patient's home. However, the use of ceftazidime for such applications is challenging in view of its relatively poor stability in solution. In this study, elastomeric infusion pumps with 6 or 7 g of ceftazidime were deflated over 24 h in an oven at 33°C while ceftazidime and its degradation product, pyridine, were regularly monitored. Hereto, a fast and sensitive liquid chromatographic (LC) method has been developed using a Kinetex C18 (150 × 3 mm, 2.6 μm) column with gradient elution. Ammonium formate 20 mM and acetonitrile (ACN) were mixed in a ratio of 98:2 v/v for mobile phase A and 85:15 v/v for mobile phase B. Both were adjusted to pH 4.5 with formic acid. The flow rate was set at 0.4 mL/min. The solution with a starting dose of 6 g ceftazidime was found to be degraded 10% after an average of 19 h 11 min so that an administration of 6 g to the patient was not reached. For the solution with a starting dose of 7 g of ceftazidime, 10% degradation was observed after an average of 18 h 42 min. However, by starting from a higher dose, an average of 6.56 g of ceftazidime could be administered over 24 h. In addition, 1.0% of pyridine versus ceftazidime pentahydrate with sodium carbonate (=mixture for injection) was formed over 24 h.
便携式输液泵是一种在患者家中继续进行门诊胃肠外抗菌治疗(OPAT)的有趣解决方案。然而,鉴于头孢他啶在溶液中的稳定性相对较差,将其用于此类应用具有挑战性。在本研究中,装有6克或7克头孢他啶的弹性输液泵在33°C的烘箱中放置24小时进行排气,同时定期监测头孢他啶及其降解产物吡啶。为此,开发了一种快速灵敏的液相色谱(LC)方法,使用Kinetex C18(150×3mm,2.6μm)色谱柱进行梯度洗脱。将20mM甲酸铵和乙腈(ACN)按98:2 v/v的比例混合作为流动相A,按85:15 v/v的比例混合作为流动相B。两者均用甲酸调节至pH 4.5。流速设定为0.4mL/min。发现起始剂量为6克头孢他啶的溶液在平均19小时11分钟后降解了10%,因此未达到向患者给药6克的剂量。对于起始剂量为7克头孢他啶的溶液,平均18小时42分钟后观察到10%的降解。然而,从更高剂量开始,24小时内平均可给予6.56克头孢他啶。此外,在24小时内,相对于头孢他啶五水合物与碳酸钠(=注射用混合物)形成了1.0%的吡啶。