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24 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 P h a r mTe c h . c o m Analytics distribution than leachable silicone oil. For accurate quantitation of leachable silicone oil, the silicone oil standard and the leachable silicone oil must have the same response factor. There are several reasons why the molecular weight and molecular weight distribution of the leachable sili- cone oil and silicone oil standards need to be different: • There are different grades (e.g., silicone oil of dif- ferent average molecular weight) of silicone oil used for the coating of container/closure compo- nents. The end-user of the prefilled syringes may not necessarily know the exact grade of silicone oil used for their products. • The molecular weight and molecular-weight dis- tribution of the leachable portion of silicone oil may not be the same as those coated on the con- tainer/closure components. For example, the high-molecular-weight portion silicone oil may not leach out the same way as the low-molecular- weight portion silicone oil. • The components of the container/closure systems may be coated with different grades of silicone oil. For example, the syringe barrel and plunger of a prefilled syringe may be coated with two dif- ferent grades of silicone oil. Therefore, the leach- able silicone oil may be a mixture of the two grades of silicone oil. To use one silicone oil standard to quantitate leach- able silicone oil of different average molecular weight and molecular-weight distribution, the response factor of the silicone oil of different average molecular weight and molecular-weight distribution must be the same or the relative response factor must be known. To evaluate the relative response factor of different silicone oils, five silicone oil standards with viscosity ranging from 50 cSt to 1000 cSt prepared at 10 ppm in xylene solution were analyzed for determining the relative response factors against the standard silicone oil of cSt 350. In addition, volatile cyclic oligomers of silicone oil— hexamethylcyclo-trisiloxane (D3), octamethyl-cyclo- tetrasiloxane (D4), and decamethyl-cyclopentasiloxane (D5)—also were evaluated for their relative response factors against the silicone oil standard. The results are summarized in Table III. The data indicate that the ICP–OES response factor of the silicone oil of different molecular weights were Table II. Inductively coupled plasma/optical emission spectrometry (ICP-OES) method conditions. Instrument Thermo iCAP 6500 Duo Plasma view Axial Analyst Si (251.611 nm) Plasma Radio frequency power 1200 W Gas flow Auxiliary (Ar) 1.0 L/min Nebulizer (Ar) 0.90 L/min Additional gas (20% O2, 80% Ar) 0.125 L/min Purge Normal Nebulizer PFA–ST microflow, 20 μL/min Injector 2.0 mm inner diameter Spray chamber Quartz Peristaltic pump Flush rate 10 rpm Sample flush time 120 seconds Pump stabilization time 15 seconds Analysis pump rate 10 rpm Diluent rinse 15 seconds Sample options Analysis mode Precision Repeats 3