Department of Engineering Chemistry, College of Engineering, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur 522 502, Andhra Pradesh, India.
Aurobindo Pharma Limited, Sanga Reddy, Indrakaran 502329, Telangana, India.
Molecules. 2022 Nov 16;27(22):7920. doi: 10.3390/molecules27227920.
Cross contamination of β-lactams is one of the highest risks for patients using pharmaceutical products. Penicillin and some non-penicillin β-lactams may cause potentially life-threatening allergic reactions. The trace detection of β-lactam antibiotics in cleaning rinse solutions of common reactors and manufacturing aids in pharmaceutical facilities is very crucial. Therefore, the common facilities adopt sophisticated cleaning procedures and develop analytical methods to assess traces of these compounds in rinsed solutions. For this, a highly sensitive and reproducible ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for the analysis of Cephapirin and Ceftiofur. As per the FDA guidelines described in FDA-2011-D-0104, the contamination of these β-lactam antibiotics must be regulated. The analysis was performed on an XBridge C18 column with 100 mm length, 4.6 mm diameter, and 3.5 µm particle size at an oven temperature of about 40 °C. The mobile phase was composed of 0.15% formic acid in water and acetonitrile as mobile phases A and B, and a flow rate was set to 0.6 mL/min. The method was validated for Cephapirin and Ceftiofur. The quantification precision and accuracy were determined to be the lowest limit of detection 0.15 parts per billion (ppb) and the lowest limit of quantification 0.4 ppb. This method was linear in the range of 0.4 to 1.5 ppb with the determination of coefficient (R2 > 0.99). This sensitive and fast method was fit-for-purpose for detecting and quantifying trace amounts of β-lactam contamination, monitoring cross contamination in facility surface cleaning, and determining the acceptable level of limits for regulatory purposes.
β-内酰胺类抗生素的交叉污染是使用药物产品的患者面临的最高风险之一。青霉素和一些非青霉素类β-内酰胺类抗生素可能引起危及生命的过敏反应。因此，在制药设施中，痕量检测普通反应器和制造助剂中β-内酰胺类抗生素的清洁冲洗液至关重要。因此，常见的设施采用复杂的清洁程序，并开发分析方法来评估冲洗溶液中这些化合物的痕量。为此，开发了一种高度灵敏且可重现的超高效液相色谱三重四极杆质谱（UHPLC-MS/MS）方法，用于分析头孢菌素和头孢噻呋。根据 FDA-2011-D-0104 中描述的 FDA 指南，必须对这些β-内酰胺类抗生素的污染进行监管。分析在 XBridge C18 柱上进行，柱长 100mm，直径 4.6mm，粒径 3.5μm，烘箱温度约为 40°C。流动相由 0.15%甲酸水溶液和乙腈作为流动相 A 和 B 组成，流速设定为 0.6mL/min。该方法经过头孢菌素和头孢噻呋的验证。精密度和准确度的定量精度确定为最低检测限 0.15 十亿分之一（ppb）和最低定量限 0.4 ppb。该方法在线性范围内 0.4 至 1.5 ppb 范围内具有良好的相关性（R2>0.99）。这种灵敏快速的方法适用于检测和定量痕量β-内酰胺污染，监测设施表面清洁中的交叉污染，并确定监管目的的可接受限量水平。
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