Quality assurance in research laboratories

During the last decade, it has become increasingly important that researchers demonstrate that research is conducted to the highest standards. The implementation of quality assurance for research laboratories will enable all fields of research and development to be judged impartially. There are no specific standards for research laboratories but where possible, existing standards can be adapted. This review is structured around two approaches. The first considers research to be a logical extension of testing, and it is assumed that testing standards can be applied methodically to each step in a research project. The second advocates a flexible approach, with research-specific criteria for assessing quality. The important papers published on this topic have been reviewed. The conclusions are that the general quality management approach, encompassed by the ISO 9000 series of standards with the emphasis on customer satisfaction and ‘fitness for purpose’, is suitable for implementing quality assurance in research laboratories.     

A system for defining reference materials applicable to all food matrices

Recently the subcommittee on Food Definition of the AOAC INTERNATIONAL Task Force on Methods for Nutrition Labeling proposed a Food Matrix Organizational System [4] to systematically judge the applicability of collaboratively studied methods over a range of food matrices. This system describes a food matrix by its location in one of nine sectors in a triangle, with each point of the triangle defined as representing 100% and the opposite side representing 0% of the normalized contents of each of three major components of FAT, PROTEIN and CARBOHYDRATE. Foods falling within the same sector would be chemically similar and thus should behave in a similar analytical manner. This same scheme can be used to select one or two food matrices representing each sector, for development of a series of reference materials representing all foods. The list of 5250 foods contained in the USDA Nutrient Data Base for Standard Reference has been sorted and matched to this schematic to determine the scope of the selection process. In addition the list of foods in the USDA Data Base for Food Consumption Surveys has been examined. Results and progress of this selection process are reported.     

A two-chromophore model for two-photon circular dichroism

A discussion of two-photon circular dichroism due to dissymmetrically placed chromophores is presented. Using quantum electrodynamics, expressions are derived for the differential rates or absorption associated with an electronic transition which is electric dipole forbidden to a one-photon interaction. A complex field formulation enables effective interaction operators to be derived which are formally equivalent to those arising in the theory of induced circular dichroism. For non-equivalent chromophores, it is shown that a coupling mechanism provides the necessary chiral discrimination, whilst for equivalent chromophores there is an additional contribution from an interference term which becomes more important as the chromophore separation is decreased.     

7-Deazaadenosine: Oligoribonucleotide building block synthesis and autocatalytic hydrolysis of base-modified hammerhead ribozymes

A 7-deazaadenosine ( = tubercidin; c⁷A; 1 ) building block for solid-phase oligoribonucleotide synthesis was prepared. The amino group of 1 was protected with the (dimethylamino)methylidene residue (→ 3 ), and the monomethoxytrityl group was introduced at OH? C(5′) (→ 4 ). Protection of OH? C(2′) was carried out by silylation, showing that use of the (i-Pr)₃Si group resulted in high 2′-O-selectivity (→ 5b , 80%). Reaction of 5b with PCl₃ afforded the phosphonate 7 which was used in solid-phase oligoribonucleotide synthesis. The autocatalytic hydrolysis of hammerhead ribozymes using pG-G-G-A-G-U-C-A-G-U-C-C-C-U-U-C-G-G-G-G-A-C-U-C-U-G-A-A-G-A-G-G-C-G-C as substrate strand (S) and modified G-C-G-C-C-G-A-A-A-C-U-C-C-C as enzyme strand (E) was studied. When c⁷A replaced A¹³ or A¹⁴, a small decrease of catalytic activity was observed, while modification in position A¹⁵ enhanced the autocatalytic hydrolysis. The results demonstrate, that the atom N(7) of adenosine in any of these positions is not crucial for ribozyme action.     

Estrogen receptor ligands. 12. Synthesis of the major metabolites of an ERalpha-selective, dihydrobenzoxathiin antagonist for osteoporosis

[reaction: see text] During the course of drug metabolism studies, a major metabolite of compound 1 was detected in rhesus monkeys and assigned structure 4. The intriguing biotransformation of 1 leading to 4 was confirmed by a 19-step total synthesis starting from resorcinol (11), the key feature of which was the construction of the oxygen bridge utilizing a phenolic oxidation and trapping sequence. In addition, the synthesis of a related metabolite (5) is described.     

Determination of lincomycin and tylosin residues in honey by liquid chromatography/tandem mass spectrometry

A simple and rapid analytical method was developed for the determination of lincomycin and tylosin residues in honey as part of field studies examining the efficacy and target animal safety of these antibiotics to control American foulbrood disease in honey bees. Residues of the antibiotics were determined using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Honey samples were diluted and injected directly into the LC/MS/MS system without additional cleanup by solid-phase extraction or liquid-liquid partitioning. A six-port valve system was utilized to selectively route eluant from the LC column into the mass spectrometer only during a relatively short portion of the chromatographic run corresponding to the elution of the analytes of interest. Minimal contamination of the MS source chamber was observed despite the analysis of large numbers of samples. Using internal standard quantitation, excellent accuracy and precision were obtained with no apparent matrix-to-matrix variation. Based on the analysis of fortified replicates, the mean percent deviation from the theoretical concentration and the percent relative standard deviation were both less than 10% for tylosin over an analytical range of 10-1000 microg/kg. Slightly higher mean percent deviations and relative standard deviations were observed for the analysis of lincomycin in fortified replicate samples. The method detection limits were determined to be 5 and 2 microg/kg for lincomycin and tylosin, respectively.     

Development of a screening method for cocaine and cocaine metabolites in urine using solvent microextraction in conjunction with gas chromatography

A simple, quick and inexpensive screening method for cocaine and cocaine metabolites has been developed. Drug extraction was achieved using the relatively new technique of solvent microextraction (SME). Complete analysis is achieved in 13 min, using, a 6-min extraction with a 2-microl drop followed by separation on a gas chromatograph. The developed procedure was tested as a screening method for cocaine and cocaine metabolites in spiked urine samples. Using SME, concentrations as low as 0.125 microg ml(-1) of cocaine, ecgonine methyl ester, cocaethylene and anhydroecgonine methyl ester were measurable with relative standard deviation values averaging 9.0%.