P R A C T I C E ~ C A S E
R E P O R T S
Assessment of trace element compatibility in total parenteral nutrition infusions M.C. A l l w o o d a n d M. G r e e n w o o d
Introduction The provision of daily total p a r e n t e r a l nutrition (TPN) needs in one large flexible bag, with or without fat emulsion, has become routine practice in m a n y countries, both for hospitalized and out-patients. Recipients of long-term feeding require m a n y micronutrients, including a number of trace elements. The list of such needs has grown with greater u n d e r s t a n d i n g and clinical experience of long-term p a r e n t e r a l feeding, and the established additives such as copper, zinc, m a g n e s i u m , iron and m a n g a n e s e are supplemented with m a n y trace elements now recognized as essential n u t r i e n t s [1]. These include chromium, selenium and m o l y b d e n u m which are currently provided in some T P N additive products, as well as v a n a d i u m , nickel, tin, arsenic, iodine and fluorine [2]. The stability and compatibility of these trace elements in total par e n t e r a l nutrition m i x t u r e s in big bags is difficult and in some cases, impossible to assess by conventional methods which depend on m e a s u r i n g concentration changes, such as atomic absorption spectroscopy. Some studies h a v e shown t h a t the major trace elements are compatible with particular mixtures. Boddapati et al. used atomic absorption spectroscopy to show t h a t zinc, copper, c h r o m i u m and m a n g a n e s e were compatible with one T P N m i x t u r e for up to 48 h at 4~ and also reported t h a t these trace elements were not retained on in-line filters [3]. A similar study confirmed the above observations using a modified T P N mixture [4]. The existence of specific incompatibilities, such as the potential for precipitation of iron phosp h a t e salts, has been recognized for m a n y years [5]. Other examples have been reported which include copper incompatibility with particular
amino acid solutions, possibly caused by the presence of cysteine [6], and the precipitation of ele m e n t a l selenium in the presence of high ascorbic acid concentrations [7]. These studies generally depended on detecting visual evidence of precipitation or falls in solution concentrations of the element of interest. However, microprecipitation can occur without a detectable concentration change, especially at the very low concentrations associated with most of the trace elements in T P N mixtures. In fact, m a n y are below the limits of m e a s u r e m e n t using standard methods, such as atomic absorption spectroscopy. The technique of X-ray energy dispersive spectroscopy (EDS) linked to an electron microscope provides a tool to examine microprecipitates collected, for example, on m e m b r a n e filters, for the presence of any element. Material retained on the filter surface can be visualized by the scanning microscope. Chosen areas of the filter are scanned by an electron b e a m which results in the generation of X-rays, whose energies are characteristic of the element(s) m a k i n g up the specimen. A detector is positioned within the microscope to collect the X-rays, which are counted and sorted by computer on the basis of their energy level. An X-ray energy spectrum of the specimen can t h e n be generated. By comparison with spectra obtained from k n o w n elements, an estimation of the elemental composition of the specimen can be made. Therefore, any precipit a t e s occurring in T P N m i x t u r e s can be collected on m e m b r a n e filters and examined by this technique, enabling the user to identify any elements contributing to the precipitate and also providing a semi-quantitative m e a s u r e of the relative amounts of each element present. The application of electron microscopy with Xr a y EDS in d e t e r m i n i n g the compatibility of
Allwood MC, Greenwood M. Assessment of trace elements compatibility in total parenteral nutrition infusions. Pharm Weekbl [Sci] 1992;14(5):321-4. Keywords Compatibility Parenteral feeding Precipitation Spectrometry, X-ray dispersive M. C. AUwood (correspondence) and 111I.Greenwood: Medicines
Research Unit and Department of Life Sciences, Derbyshire College of Higher Education, Mickleover, Derby DE3 5GX, United Kingdom.
14(5) 1992
Abstract The application of X-ray energy dispersive spectroscopy to detect elements collected from TPN mixtures on membrane filters has been investigated. Many simple total parenteral nutrition mixtures prepared aseptically in large bags can be stored for extended periods. Trace elements are normally excluded from such bags, because not enough is known about their long-term stability and compatibility in total parenteral nutrition mixtures. Assessing the compatibility of many trace elements by conventional methods that rely on detecting concentration changes is extremely difficult. Analysis of precipitates from total parenteral nutrition mixtures confirmed that the proposed method was capable of identifying a number of elements from the mixture in complex precipitates, including calcium, phosphorus, iron, copper and selenium.
Accepted June 1992.
P h a r m a c e u t i s c h Weekblad Scientific edition
321
X-RAY: Live= Real:
0 - 20 keU 500s Preset= 500s R e m a i n i n g : 633s 21% Dead
Os
SC Figure 1
X-ray EDS scan of the surface of a membrane filter washed with water for irrigations. Peaks caused by Si, S and C1 are indicated
F=
R E P O R T S
Assessment of trace element compatibility in total parenteral nutrition infusions M.C. A l l w o o d a n d M. G r e e n w o o d
Introduction The provision of daily total p a r e n t e r a l nutrition (TPN) needs in one large flexible bag, with or without fat emulsion, has become routine practice in m a n y countries, both for hospitalized and out-patients. Recipients of long-term feeding require m a n y micronutrients, including a number of trace elements. The list of such needs has grown with greater u n d e r s t a n d i n g and clinical experience of long-term p a r e n t e r a l feeding, and the established additives such as copper, zinc, m a g n e s i u m , iron and m a n g a n e s e are supplemented with m a n y trace elements now recognized as essential n u t r i e n t s [1]. These include chromium, selenium and m o l y b d e n u m which are currently provided in some T P N additive products, as well as v a n a d i u m , nickel, tin, arsenic, iodine and fluorine [2]. The stability and compatibility of these trace elements in total par e n t e r a l nutrition m i x t u r e s in big bags is difficult and in some cases, impossible to assess by conventional methods which depend on m e a s u r i n g concentration changes, such as atomic absorption spectroscopy. Some studies h a v e shown t h a t the major trace elements are compatible with particular mixtures. Boddapati et al. used atomic absorption spectroscopy to show t h a t zinc, copper, c h r o m i u m and m a n g a n e s e were compatible with one T P N m i x t u r e for up to 48 h at 4~ and also reported t h a t these trace elements were not retained on in-line filters [3]. A similar study confirmed the above observations using a modified T P N mixture [4]. The existence of specific incompatibilities, such as the potential for precipitation of iron phosp h a t e salts, has been recognized for m a n y years [5]. Other examples have been reported which include copper incompatibility with particular
amino acid solutions, possibly caused by the presence of cysteine [6], and the precipitation of ele m e n t a l selenium in the presence of high ascorbic acid concentrations [7]. These studies generally depended on detecting visual evidence of precipitation or falls in solution concentrations of the element of interest. However, microprecipitation can occur without a detectable concentration change, especially at the very low concentrations associated with most of the trace elements in T P N mixtures. In fact, m a n y are below the limits of m e a s u r e m e n t using standard methods, such as atomic absorption spectroscopy. The technique of X-ray energy dispersive spectroscopy (EDS) linked to an electron microscope provides a tool to examine microprecipitates collected, for example, on m e m b r a n e filters, for the presence of any element. Material retained on the filter surface can be visualized by the scanning microscope. Chosen areas of the filter are scanned by an electron b e a m which results in the generation of X-rays, whose energies are characteristic of the element(s) m a k i n g up the specimen. A detector is positioned within the microscope to collect the X-rays, which are counted and sorted by computer on the basis of their energy level. An X-ray energy spectrum of the specimen can t h e n be generated. By comparison with spectra obtained from k n o w n elements, an estimation of the elemental composition of the specimen can be made. Therefore, any precipit a t e s occurring in T P N m i x t u r e s can be collected on m e m b r a n e filters and examined by this technique, enabling the user to identify any elements contributing to the precipitate and also providing a semi-quantitative m e a s u r e of the relative amounts of each element present. The application of electron microscopy with Xr a y EDS in d e t e r m i n i n g the compatibility of
Allwood MC, Greenwood M. Assessment of trace elements compatibility in total parenteral nutrition infusions. Pharm Weekbl [Sci] 1992;14(5):321-4. Keywords Compatibility Parenteral feeding Precipitation Spectrometry, X-ray dispersive M. C. AUwood (correspondence) and 111I.Greenwood: Medicines
Research Unit and Department of Life Sciences, Derbyshire College of Higher Education, Mickleover, Derby DE3 5GX, United Kingdom.
14(5) 1992
Abstract The application of X-ray energy dispersive spectroscopy to detect elements collected from TPN mixtures on membrane filters has been investigated. Many simple total parenteral nutrition mixtures prepared aseptically in large bags can be stored for extended periods. Trace elements are normally excluded from such bags, because not enough is known about their long-term stability and compatibility in total parenteral nutrition mixtures. Assessing the compatibility of many trace elements by conventional methods that rely on detecting concentration changes is extremely difficult. Analysis of precipitates from total parenteral nutrition mixtures confirmed that the proposed method was capable of identifying a number of elements from the mixture in complex precipitates, including calcium, phosphorus, iron, copper and selenium.
Accepted June 1992.
P h a r m a c e u t i s c h Weekblad Scientific edition
321
X-RAY: Live= Real:
0 - 20 keU 500s Preset= 500s R e m a i n i n g : 633s 21% Dead
Os
SC Figure 1
X-ray EDS scan of the surface of a membrane filter washed with water for irrigations. Peaks caused by Si, S and C1 are indicated
F=
