REPORT FOR ANALYSTS
PORTABLE
DC VTVM has 200 microvolt and 10
u
sensitivity
ohms input
T H I S little instrument measures transistor and electrochemical potentials, voltages of charged capacitors and dc amplifiers, and voltages at the summing points of analog computers. It can be most useful in measuring low currents in semiconductors, ion chambers, and photocells. It also may be used to test insulation leakage and volume resistivity.
KEITHLEY MODEL 200B
DC VTVM
BATTERY-OPERATED, the Model 200B has voltage ranges of 0.008, 0.02, 0.08, 0.2, 0.8, 2, 8 and 20 volts full scale of either polarity. Accuracy is within 2 %. Accessories permit measuring currents as low as 5 * 10"14 ampere, resistances above 1016 ohms and voltages up to 20 kv. D E S I G N F E A T U R E S include excellent zero stability, a polarity reversing switch, 500 hours useful battery life, and a constant zero from range to range. DETAILED DATA on the Model 200B is now available in Keithley Engineering Notes, Vol. 4 No. 1. Your copy will be sent promptly upon request on your company letterhead.
KEITHLEY INSTRUMENTS, INC. 12415Euclid Ave, Cleveland6, Ohio Circle No. 22 A on Readers' Service Card, page 73 A
22 A
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ANALYTICAL CHEMISTRY
factors, he m a y find himself completely inaccurate in his final conclusion. F o r example, certain tests in t h e monographs on amobarbital, phénobarbital, amobarbital sodium, phénobarbital sodium, and secobarbital sodium read identically t h e same. T h e chemist m u s t also realize t h a t , frequently, classical identity tests as specified in control specifications cover only a general field of products a n d are not specific for a n y one member within the field. F o r example, it m a y be noted t h a t ascorbic acid reduces Fehling's solution. This does n o t mean, as might be inferred if t h e single identification test were t a k e n as a criterion of identity, t h a t t h e product being tested can be only ascorbic acid, since Fehling's solution will be reduced b y a n y reducing substance, even a solution of glucose. A similar degree of nonspecificity was indicated recently in t h e proposed control specifications for reserpine. T h e identification tests as proposed would have given positive results for practically all of t h e known alkaloids extracted from rauwolfia species. T h u s t h e challenge is thrown t o t h e control chemists t o establish control tests of i d e n t i t y on t h e various new chemicals coming o u t of research today, tests of identity which are specific for t h e product a n d which are n o t affected adversely b y small a m o u n t s of impurities which m a y give rise t o false i m pressions. Purity Tests. Purity tests are subj e c t t o m a n y of t h e variables n o t e d in i d e n t i t y t e s t s . T h e old classical g r a v i m e t r i c or t i t r i m e t r i c d e t e r m i n a t i o n s m a y b e subject t o error, giving a false sense of security t o t h e chemist who is analyzing a fine chemical or a new pharmaceutical product. Coprecipitation of impurities with t h e desired constituent in gravimetric assays has troubled t h e chemist for m a n y years. Fleeting end points in titrimetric procedures m a y cause variations from chemist t o chemist and laboratory t o laboratory. T h e determination of total alkalinity of racemic p a n t o t h e n a t e m a y v a r y b y as m u c h as 0.2 ml. of O.liV hydrochloric acid using phenolphthalein as t h e indicator, owing t o t h e rate of titration as carried out b y t h e chemist making t h e determination. I n order t o avoid this variation, t h e control procedure h a s been changed t o direct t h e addition of t h e m a x i m u m permissible a m o u n t of acid, after which two drops of phenolphthalein are added and " n o pink color is produced within 5 seconds." Classical p u r i t y tests m a y often provide insufficient information for proper control. I n t h e paper b y Strode, Stewart, Schott, and Caldwell (S) t h e s t a t e m e n t was m a d e " t h e U S P limit test for free salicylic acid in aoetylsalicylic acid a n d
aspirin tablets does n o t provide sufficient information for manufacturing process control." P u r i t y tests frequently a r e n o t specific for a single ingredient or a single member of a family of compounds which m i g h t be present. Schulz a n d Neuss (4) noted t h a t current methods employed in determination of corticosteroids fail t o distinguish between t h e hydrocortisones a n d cortisones. Likewise, in our experience, we have seen methods fail t o distinguish between reserpine a n d deserpidine p r o d u c t s . About six m o n t h s ago, during t h e manufacture of a pharmaceutical formulation, it was noted t h a t occasional lots of U S P diethylstilbestrol were not completely soluble in a vegetable oil. N o a p p a r e n t deviation from U S P s t a n d a r d s could be found. T h e analytical research chemists in our laboratory went t o work on t h e problem and within a few m o n t h s determined t h a t t h e p u r i t y test for diethylstilbestrol as specified in U S P X V is n o t specific for pure diethylstilbestrol a n d will include in t h e total weight of t h e precipitate formed a t least three other products which are either beginning raw materials in t h e synthesis or by-products of t h e synthesis. Knowing t h e nonspecificity of t h e p u r i t y assay, our chemists were soon able t o work out a p u r i t y assay which determines only t h e pure diethylstilbestrol present. T h e m e t h ods will be mentioned later. Effects of I m p u r i t i e s . L e t us consider t h e effects of i m p u r i t i e s n o t d e t e c t e d b y o u r classical a s s a y a n d t h e effects of nonspecificity of i d e n t i t y t e s t s which a r e c u r r e n t l y used for m a n y p r o d u c t s of p h a r m a c e u t i c a l a n d fine chemical m a n u f a c t u r i n g t o d a y . I m p u r i t i e s in certain r a w m a t e r i a l s often m a t e r i a l l y reduce yields a n d s t a b i l i t y of p h a r m a c e u t i c a l formulations. M a n y pharmaceutical formulations t o d a y are prepared through t h e skill of t h e pharmaceutical chemists in compounding together a large n u m b e r of incompatible drugs a n d vitamins. I know of a case recently where m a n y tens of thousands of dollars worth of a multivitamin pharmaceutical formulation h a d to be rejected because of t h e presence of an unexpected impurity in one of t h e raw materials which went into t h e formulation, a n i m p u r i t y which did n o t cause too m u c h trouble while t h e raw material was in a d r y condition b u t which resulted in almost complete deterioration of t h e vitamin in a m a t t e r of a few days when p u t into t h e specific pharmaceutical formulation. Unforeseen impurities can have a tremendous effect on t h e stability of even raw materials. Impurities in aoetylsalicylic acid, for example, can
