An Analytical Procedure by the Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for the Quantitation of Total Phosphorus Content on the Surface of the Manufacturing Equipment for Oligonucleotides

An analytical procedure by the inductively coupled plasma mass spectrometry (ICP-MS) is provided to quantitate the remaining phosphorus amount on the surface of the manufacturing equipment for the oligonucleotide active pharmaceutical ingredient (API). In this analytical procedure, the sample solutions obtained from the rinse sampling and direct surface sampling methods are directly injected into the ICP-MS equipment without the inspissation of the extraction liquid. The limit of quantitation for phosphorous was 0.02 µg/mL. Quantitation of phosphorous was achieved over a linear range of 0.02 to 0.8 µg/mL. Analytical validation was carried out to prove that this analytical procedure is appropriate and effective to monitor the cleanliness of the manufacturing equipment after the oligonucleotide API manufacturing and the following cleaning of the equipment. Calibration curve originally passed through the origin with correlation coefficient of 0.999. The precision through the rinse sampling method was within ±10%. The satisfactory accuracy for the rinse sampling method was proven from the assessment of linearity and precision. The precision and accuracy of the analytical procedure were both within ±10% for the direct surface sampling method. The described analytical procedure by ICP-MS following the two types of the sampling procedures can easily be applied to the routine analysis for the verification of the cleanliness of the manufacturing equipment for oligonucleotide API.