A quality systems approach for identifying and controlling sources of error with point of care testing devices

Historically, due to the size and nature of the instrumentation, highly skilled laboratory professionals performed clinical testing in centralized laboratories. Today’s clinicians demand realtime test data at the point of care. This has led to a new generation of compact, portable instruments permitting ”laboratory” testing to be performed at or near the patient’s bedside by nonlaboratory workers who are unfamiliar with testing practices. Poorly controlled testing processes leading to poor quality test results are an insidious problem facing point of care testing today. Manufacturers are addressing this issue through instrument design. Providers of clinical test results, regardless of location, working with manufacturers and regulators must create and manage complete test systems that eliminate or minimize sources of error. The National Committee for Clinical Laboratory Standards (NCCLS) in its EP18 guideline, ”Quality management for unit-use testing,” has developed a quality management system approach specifically for test devices used for point of care testing (POCT). Simply stated, EP18 utilizes a ”sources of error” matrix to identify and address potential errors that can impact the test result. The key is the quality systems approach where all stakeholders – professionals, manufacturers and regulators – collaboratively seek ways to manage errors and ensure quality. We illustrate the use of one quality systems approach, EP18, as a means to advance the quality of test results at point of care. Received: 26 June, 2002 Accepted: 17 July 2002 Presented at the European Conference on Quality in the Spotlight in Medical Laboratories, 7–9 October 2001, Antwerp, Belgium Abbreviations NCCLS National Committee for Clinical Laboratory Standards (formerly) · POCT point of care testing · QC quality control · HACCP hazard analysis critical control points · CLIA clinical laboratory improvement amendments (of 1988) Correspondence to S. S. Ehrmeyer     

Quality management, certification and accreditation in medical laboratories – the view of ECLM

 Increasing demands from health care planners and industrialists conducting clinical trials, as well as general competition, are forcing medical laboratories to seek third-party recognition of their quality management systems. There is a tendency to move from certification of a laboratory director, via certification of the laboratory quality system (ISO 9000 family), to accreditation needing proof of professional and technical competence in laboratory tasks. The requirements of accreditation are presented in several national schemes and in the European Standards series (EN 45 000) and the International Organization for Standardization's guide, ISO/IEC 25, to be amalgamated soon. The latter system provides transnational recognition through participation of the accrediting bodies in the European co-operation for Accreditation. Necessary supplementary guidelines exist for chemical laboratories (Eurachem) and medical laboratories CEAC/ECLM). Traceability and reliability of results are obtained by utilizing a global reference examination system and by participating in transdisciplinary work. The costs of achieving accreditation are considerable and mainly involve the production of quality handbooks and written work procedures by personnel. The rewards are an open system, smoother work, emphasis on prevention of mistakes, and satisfied stakeholders. Received: 5 October 1998 · Accepted: 20 October 1998     

EAL interlaboratory comparison Wa1 – Testing of potable water

 The accreditation of laboratories has emphasized the use of interlaboratory comparisons as a tool to monitor the comparability and accuracy of results laboratories produce. An interlaboratory comparison for water laboratories was organized among European Cooperation for Accreditation (EA) member countries; 30 laboratories, 7 of which were not accredited, from 14 European countries participated in this intercomparison. All the laboratories were chosen by the appropriate national accreditation bodies, with the instruction to select as participants those laboratories which act as national reference laboratories in this field. About 90% of the data collected was considered satisfactory after statistical treatment. Non-accredited laboratories performed as well as accredited laboratories. The laboratories were asked to take corrective action and report the corrections to the accreditation bodies. A great variation in the reported uncertainties of the results was observed. There seems to be a need to organize EA interlaboratory comparisons for national reference laboratories analysing water. It is obvious that even reference laboratories need training in how to estimate the uncertainty of results. Received: 22 July 1998 · Accepted: 21 September 1998     

Telematics applications in a laboratory cluster

 The laboratories of six hospitals in the Canton of Wallis in Switzerland have been connected to one central laboratory, using the same database, the same software applications for the laboratory, pathology and pharmacy, and the same office and administration software. Some instruments in "Point of Care" sites are online for result transmission and for telemaintenance. The physicians may order drugs, material for sampling, analyses for specified patients and may consult knowledge bases, the patient data base, results and reports in different formats (ASCII, HTML, PDF, JPG, GIF, ...) using browsers like Netscape or MS-Explorer. To guarantee privacy, the access is restricted and protected by user-name, password and firewall. This report describes conditions for a successful introduction and usage of quality management through laboratory telematics. Received: 15 April 2000 · Accepted: 15 April 2000     

A view of uncertainty at the bench analytical level

 The problem with which analytical laboratories are confronted, after traceability of their results has been demonstrated, is correctly estimating their uncertainty– to which traceability is also to some extent subject. While the general principles for calculating the uncertainty of physical measurements are applicable to chemical metrology, some refinements are needed, especially careful selection and planning the level at which uncertainty will be estimated by each laboratory in accordance with its capacity and required demands. Depending on the particular decision to be made, the mechanism to be used to estimate the uncertainty varies markedly; also, the rigour of the estimation increases with increasing stringency of the demands. This paper describes the primary sources of uncertainty in chemical metrology and discusses different approaches to its estimation in relation to the type of analytical laboratory concerned. The view presented tries to be close to the bench analytical level, in order to be practical and flexible for laboratories, although it could sometimes be considered slightly heterodox. Received: 25 March 1997 · Accepted: 20 September 1997     

Basic steps towards a self-sustainable quality system and laboratory accreditation

 Laboratory managers are facing the task of altering the attitudes of themselves and their employees in order to implement a quality lifestyle, which is the prerequisite for successful implementation of a quality system complying with appropriate international standards. The alterations require a painstaking and constructive approach. Not all laboratories have the resources to secure the assistance of quality consultants. For those laboratory managers who have to find their way towards quality management on their own, some recommendations are given for a path towards a self-sustaining quality system. Several practical aspects of the basic steps in this path, which starts with assessing the current status of the laboratory and is followed by awareness building, are discussed. The recommendations are derived from the experience of the authors in their own laboratories. Received: 5 June 1997 · Accepted: 7 December 1997     

Syntheses,weak interactions, 3D network structures and magnetic properties of two salts based on bis(maleonitriledithiolate)copper(II) anion and substituted triphenylphosphonium cation

Two new salts, [BzTPP]₂[Cu(mnt)₂] (1) and [4NO₂BzTPP]₂[Cu(mnt)₂] (2) (BzTPP⁺ = benzyltriphenylphosphonium and mnt²⁻ = maleonitriledithiolate) have been prepared and characterized by elemental analyses, UV, IR, molar conductivity and single-crystal X-ray diffraction. The single-crystal structure analysis shows that 1 crystallizes in the monoclinic space group P2₁/n, while 2 crystallizes in the triclinic space group P−1. The effects of weak intramolecular interactions such as C–H···O, C–H···S, C–H···N, C–H···Cu hydrogen bonds and p···π, π···π stacking interactions in the solids generate a 3D network structure. It is noted that the change in the molecular topology of the counteraction when the 4-substituted group in the benzyl ring is changed from H to NO₂ results in differences in the crystal system, space group, weak interactions and the stacking mode of the cations and anions of 1 and 2. The magnetic susceptibilities of these salts measured in the temperature range 2.0 to 300 K show weak ferromagnetic coupling features with θ = 2.05 × 10⁻² K for 1 and 5.13 × 10⁻³ K for 2.     

A theoretical investigation of (−)-deprenyl (selegiline) as a radical scavenger

The chemical reactions between (−)-deprenyl and ·OH or ·OOH were studied using molecular orbital theory, with N,N-dimethylpropargylamine as a model. (−)-Deprenyl was confirmed to be a good radical scavenger. The active site was the acetylenic part and ·OH- or ·OOH was trapped on either acetylenic carbon. The activation energies were about 10–20 kcal/mol. The resulting ·OH- or ·OOH-adducts, still radicals, trapped further radicals on the remaining carbon of the acetylenic part. The final double trapping products were at extraordinarily lower energy levels than the original reactants by 50–70 kcal/mol. The secondary transition states were not detected, suggesting that the reactions occurred at once or in a cascade. Some results with the model system were verified by the results with the real (−)-deprenyl system. Received: 6 October 1999 / Accepted: 5 March 2000 / Published online: 21 June 2000     

X-ray crystal structures of halogen containing nucleobase derivatives in unsolvated and DMSO solvated forms

A series of halogenated nucleobase derivatives 1–4 is reported to yield solvent-free (2) and DMSO solvated crystals (1, 3, 4) on the crystallization from DMSO with one of them (4) containing an additional molecule of water. The molecular and crystal structures are described and comparatively discussed with reference to previous results on related compounds. The molecule of 1 is planar, molecules of 2 and 3 show syn alignment with reference to the heterocyclic ring and common C2′-endo conformation of the ribose residue, while 4 is also syn aligned but C4′-exo in the sugar conformation. The packing structures reveal typical aggregations created via networks of hydrogen bonds. These involve conventional N–H···N, N–H···O and O–H···O interactions between nucleobase and ribose units as well as solvent molecules, additionally supported by weak C–H···O contacts but excluding the participation of halogen···halogen interactions as well as halogen···heteroatom contacts in the supramolecular structure formation.     

Syntheses, crystal structures, and properties of two salts based on Ni(mnt)2 (mnt2− = maleonitriledithiolate) anion and substituted triphenylphosphonium cation

Two new salts, [oClBzTPP]₂⁺[Ni(mnt)₂]²⁻(1) and [oClBzTPP]⁺[Ni(mnt)₂]⁻(2) ([oClBzTPP]⁺ = 1-(2′-chlorobenzyl)triphenylphosphonium and mnt²⁻ = maleonitriledithiolate) have been prepared and characterized by elemental analyses, UV, IR, MS spectra, single crystal X-ray diffraction, and magnetic susceptibility. The Ni ions of the Ni(mnt)₂ anions for 1 and 2 exhibit the square-planar coordination geometry. The Ni(III) ions of 2 form a 1D zigzag alternating magnetic chain within a Ni(mnt)₂⁻ column through Ni···S, S···S, or Ni···Ni interactions. The C–H···N, C–H···S, C–H···π hydrogen bonds or π···π stacking interactions play important roles in the molecular stabilizing and stacking of 1 and 2. Magnetic susceptibility measurements in the temperature range 1.8−300 K show that 2 exhibits diamagnetic behavior.     

Preparation and Radical Oligomerization of anFe(II) Complex without Loss of Spin-Crossover Properties

 11-(4H-1,2,4-Triazol-4-yl)-undecylmethacrylate (1), a new ligand for Fe(II) spin-crossover (SCO) complexes containing a polymerizable group, was synthesized and characterized. The complex [Fe·1 ₃](BF₄)₂ (2) was obtained by reaction of 1 with Fe(BF₄)₂·6H₂O (molar ratio 1/Fe(II) = 3/1) in THF. Complex 2 showed a gradual spin-crossover between 80 and 230 K. The methacrylate units in the ligands of complex 2 could be oligomerized radically in solution (initiator: azoisobutyronitrile) without loss of the spin-crossover behaviour.     

Synthesis and structural studies of C-5 aryl- and C-6 alkyl-substituted pyrimidine derivatives

C-5 and C-6 disubstituted pyrimidine derivatives 2–7 were synthesized. Introduction of the aryl rings at C-5 of pyrimidine moiety in 5 and 6 was performed using palladium-catalyzed Stille cross-coupling reaction. The novel C-6 fluorophenylalkylated 5-phenylpyrimidine derivative (7) was prepared by lithiation of 5-phenylpyrimidine (6) and subsequent reaction of thus obtained organolithium intermediate with p-fluoroacetophenone. The structures of 3, 4 and 6 were determined by X-ray crystal structure analysis. Both methoxy groups in these structures adopt a synperiplanar conformation with respect to the N1 and N3 atoms of the pyrimidine ring. The molecules of 3 and 4 are linked through weak Br···Br interactions into zig-zag chains. The molecules of 6 are assembled into layers by one C–H···O hydrogen bond, C–H···π and aromatic π···π stacking interactions.     

Preparation and certification of JAC river water reference material for trace element analysis

 The Japan Society for Analytical Chemistry has recently issued a river water-certified reference material (CRM) for use in the ultratrace analysis of elements in fresh water. The river water CRM consists of a set of two (natural and spiked) 500-ml samples. The natural water is certified for Pb, Cr, As, Cu, Fe, Mn, Zn, B and Al at their sub-μg/l levels, while the spiked water is intended for use in the regulatory analysis of tap water and fresh water. Key words River water · Trace element analysis · Regulatory analysis · Reference materials     

Extraction and <Emphasis Type="Italic">ab initio</Emphasis> calculation studies on the complexation of Ca<Superscript>2+</Superscript> with valinomycin

From extraction experiments and γ-activity measurements, the exchange extraction constant corresponding to the equilibrium Ca²⁺ (aq)+1·Sr²⁺ (nb) ⇆ 1·Ca²⁺ (nb) + Sr²⁺ (aq) taking place in the two-phase water-nitrobenzene system (1 = valinomycin; aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log K _ex (Ca²⁺, 1·Sr²⁺) = 2.4±0.1. Further, the stability constant of the valinomycin-calcium complex (abbrev. 1·Ca²⁺) in nitrobenzene saturated with water was calculated for a temperature of 25 °C: log β _nb (1·Ca²⁺) = 8.3±0.1. By using quantum mechanical DFT calculations, the most probable structure of the 1·Ca²⁺·2H₂O complex species was predicted. In this complex, the “central” Ca²⁺ cation is bound by strong bonds to two oxygen atoms of the respective water molecules and to four ester carbonyl oxygens of the parent valinomycin ligand 1. Finally, the calculated binding energy of the considered complex 1·Ca²⁺·2H₂O is −319.2 kcal/mol, which confirms the relatively high stability of this cationic complex species.     

Chemistry of the Thermal Decomposition of Lutetium Selenities

 The solubility isotherm of the system Lu₂O₃–SeO₂–H₂O was studied at 100°C. The compounds of the three-component system were identified by Schreinemakers’ method and chemical, derivatograph and X-ray phase analyses after separation in the pure state: Lu₂(SeO₃)₃·4H₂O and LuH(SeO₃)₂·2H₂O.     

Experimental Evidence for a Calix[4]arene-Proton Complex

Summary. From extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium H⁺(aq) + 1 ·Na⁺(nb) ⇆ 1 ·H⁺(nb) + Na⁺(aq) taking place in the two-phase water-nitrobenzene system (1 = p-tert-butylcalix[4]arene-tetrakis(N, N-diethylacetamide); aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log K _ex(H⁺, 1 ·Na⁺) = −1.4 ± 0.1. Further, the stability constant of the p-tert-butylcalix[4]arene-tetrakis(N,N-diethylacetamide)-H⁺ complex in water saturated nitrobenzene was calculated for a temperature of 25°C as log β_nb(1 · H⁺) = 8.1 ± 0.1.     

三角柔性多羧酸金属有机骨架化合物的合成、结构及荧光性质

以柔性1,3,5-三（4-羧酸苯氧基）苯（H₃TCPB）为配体,以4,4''-联吡啶（4,4''-BPY）为辅助配体,在溶剂热条件下合成了2个新颖的分别具有三核锌簇和三核钴簇的金属有机骨架化合物：{[Zn₃（TCPB）₂（4,4''-BPY）]·DMF·3H₂O}_n（1）和{[Co_1.5（TCPB）（DMF）（H₂O）]·DMF}_n（2）,通过单晶X射线衍射,红外光谱,元素分析,热重分析和粉末X射线衍射对其结构进行了表征。单晶X射线衍射分析表明化合物1属于三斜晶系,P1空间群,表现出三维（3,8）连接的网状结构,拓扑符号为：{4³}₂·{4⁶·6¹⁸·8⁴}·{6};化合物2也属于三斜晶系,P1空间群,为二维（3,6）连接的网络层状结构,拓扑符号为：{4³}₄·{4⁶·6¹⁸·8⁴}。此外,荧光性质研究表明固态化合物¹在室温条件下发射出源于TCPB^3-和4,4''-BPY配体的淡蓝色荧光,而化合物2在相似的条件下没有荧光发射。     

Preparation and Radical Oligomerization of anFe(II) Complex without Loss of Spin-Crossover Properties

Summary.  11-(4H-1,2,4-Triazol-4-yl)-undecylmethacrylate (1), a new ligand for Fe(II) spin-crossover (SCO) complexes containing a polymerizable group, was synthesized and characterized. The complex [Fe·1 ₃](BF₄)₂ (2) was obtained by reaction of 1 with Fe(BF₄)₂·6H₂O (molar ratio 1/Fe(II) = 3/1) in THF. Complex 2 showed a gradual spin-crossover between 80 and 230 K. The methacrylate units in the ligands of complex 2 could be oligomerized radically in solution (initiator: azoisobutyronitrile) without loss of the spin-crossover behaviour. Received May 30, 2000. Accepted December 10, 2000     

Mechanistic aspects of the substrate ionization step in aminium salt catalyzed cyclopropanation

The cyclopropanations of a series of m- and p-substituted trans-β-methylstyrenes (3) by ethyl diazoacetate (4), catalyzed by tris(4-bromophenyl)aminium hexachloroantimonate (1 ^·+) and also by tris(2,4-dibromphenyl) aminium hexachloroantimonate (2 ^·+) have been studied by competition kinetics. For the reactions catalyzed by the milder aminium salt (1 ^·+), the Hammett-Brown ρ values and the fact that the absolute rates are independent of the concentration of 4 establish that ionization to 3 ^·+ is not reversible, but rate-determining. The dependence of the magnitude of ρ upon the absolute concentration of 3 indicates the operation of competing chain and catalytic mechanisms, i.e. the ionization of 3 by both product cation radicals and by the catalyst. The extremely low ρ value observed in the reactions catalyzed by 2 ^·+ indicates the exclusive operation of a relatively unselective chain mechanism. These mechanistic assignments are further supported by the observation of the formation of the same products under electrochemical conditions, in the absence of a chemical catalyst, in closely comparable diastereoisomer ratios and with ρ values which correspond nicely with the ρ values observed for equipotential aminium salt catalysts.     

Crystallographic and theoretical studies of 4,4′-dimethyl-7,7′-bi([1,2,5]thiadiazolo[3,4-b]pyridylidene)–chloranilic acid (1/1) with intermolecular O–H···N hydrogen bonds and S···O heteroatom interactions

Abstract  The molecular and crystal structure of a 1:1 co-crystal of 4,4′-dimethyl-7,7′-bi([1,2,5]thiadiazolo[3,4-b]pyridylidene)–chloranilic acid, (1), has been determined by X-ray diffraction at the monoclinic space group P2₁/c with cell parameters of a = 8.422(6), b = 7.343(4), c = 16.112(7) ?, β = 104.988(8)°, V = 962.5(10) ?³ and Z = 2. In the crystal structure, two components connect via the intermolecular O–H···N hydrogen bonds [2.804(4) ?] and S···O heteroatom interaction [2.945(3) ?] with R ₂ ²(7) couplings to form a unique and infinite one-dimensional supramolecular tape structure. The calculations of (1) at the HF/6-31G(d), MP2/6-31G(d), and B3LYP/6-31G(d) levels can almost reproduce X-ray geometry. In addition, the distances of the intermolecular O–H···N and S···O interactions by MP2/6-31G(d) and B3LYP/6-31G(d) levels agree well with those in the crystal. The calculated binding energies corrected BSSE and ZPE are −4.487 (HF), −7.473 (MP2), and −5.640 (B3LYP) kcal/mol. The results suggest that the complex (1) is very stable and the dispersion interaction is significantly important for the attractive intermolecular interaction in (1). The NBO analysis has revealed that the n(N) → σ*(O–H) interaction gives the strongest stabilization to the system and the major interaction for the intermolecular S···O contact is n(O) → σ*(S–N). Index Abstract  In the crystal structure of the title compound, the molecules are linked by intermolecular O–H···N hydrogen bonds and short S···O heteroatom interactions with R ₂ ²(7) couplings to construct a unique and infinite one-dimensional supramolecular tape structure.