Standard operating procedure method transfer

Before the planning of any transfer, an approved document that describes both the general transfer process as well as the specific acceptance criteria necessary for the method(s) being transferred needs to be in place. In many companies, it is common for both the R D and quality units to have general standard operating procedures (SOPs) that govern the transfer process. These SOPs describe the details of a method transfer protocol that is specific to the product and methods. The contents of such a protocol were described in various chapters earlier in this text however, they are important and bear repeating here. 

Three control methods are used on each bead-end system. First, the poison is mixed according to standard operating procedures and the measurements are affirmed by the operator s supervisor. Second, the poisoned solution is stirred, sampled, analyzed, and the analysis reported while still in the mix tank, Finally, a Nuclear Poison Detection System (NPDS) must show an acceptable poison concentration before the solution can be transferred. The NPDS provides a continuous monitoring of the boron concentration in the solution and automatic alarm and shutoff of the acid feed valves should the... 

Procedure (iodometric method). Weigh out accurately about 5.0 g of the bleaching powder into a clean glass mortar. Add a little water, and rub the mixture to a smooth paste. Add a little more water, triturate with the pestle, allow the mixture to settle, and pour off the milky liquid into a 500 mL graduated flask. Grind the residue with a little more water, and repeat the operation until the whole of the sample has been transferred to the flask either in solution or in a state of very fine suspension, and the mortar washed quite clean. The flask is then filled to the mark with distilled water, well shaken, and 50.0 mL of the turbid liquid immediately withdrawn with a pipette. This is transferred to a 250 mL conical flask, 25 mL of water added, followed by 2 g of iodate-free potassium iodide (or 20 mL of a 10 per cent solution) and 10 mL of glacial acetic acid. Titrate the liberated iodine with standard 0.1M sodium thiosulphate. 

If methods are used in which the overall recovery is 70% or above, and if the possibility of accidental but undetected very large losses is reduced by using a minimum of steps and transfer operations, or by automation, it is questionable whether in practice the precision will be greatly increased by current techniques of using internal radioactive standards. In the case of many urinaiy steroids, conjugated internal standards would be required for full control of the procedure and are not yet generally available. Finally the technique itself is not error-free, even in the absence of isotope effects, and the usual techniques employed so far often involve very small volumes of volatile solvents in which transfer errors can be large unless very superior manual technique is used. 

Various methods for the preparation of dichlorophenylborane, C H5BCl2, have been reported but the interaction of tetraphenylstannane with boron trichloride is the most commonly adopted procedure. Although an almost complete phenyl transfer from tin to boron occurs in the absence of solvent, the standard preparation employs benzene as solvent but utilizes only two phenyl groups of the tetraphenylstannane. Since the reaction has been reported to be very vigorous in the absence of solvent, this latter method is limited to the preparation of small quantities of dichlorophenylborane. However, under appropriate conditions the process based on the above equation may be applied to large-scale operations without difficulty. 

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