Field evaluations of the VDmax approach for substantiation of a 25 kGy sterilization dose and its application to other preselected doses

The International and European standards for radiation sterilization require evidence of the effectiveness of a minimum sterilization dose of 25 kGy but do not provide detailed guidance on how this evidence can be generated. An approach, designated VD_max, has recently been described and computer evaluated to provide safe and unambiguous substantiation of a 25 kGy sterilization dose. The approach has been further developed into a practical method, which has been subjected to field evaluations at three manufacturing facilities which produce different types of medical devices. The three facilities each used a different overall evaluation strategy: Facility A used VD_max for quarterly dose audits; Facility B compared VD_max and Method 1 in side-by-side parallel experiments; and Facility C, a new facility at start-up, used VD_max for initial substantiation of 25 kGy and subsequent quarterly dose audits. A common element at all three facilities was the use of 10 product units for irradiation in the verification dose experiment.

The field evaluations of the VD_max method were successful at all three facilities; they included many different types of medical devices/product families with a wide range of average bioburden and sample item portion values used in the verification dose experiments. Overall, around 500 verification dose experiments were performed and no failures were observed. In the side-by-side parallel experiments, the outcomes of the VD_max experiments were consistent with the outcomes observed with Method 1.

The VD_max approach has been extended to sterilization doses >25 and <25 kGy; verification doses have been derived for sterilization doses of 15, 20, 30, and 35 kGy. Widespread application of the VD_max method for doses other than 25 kGy must await controlled field evaluations and the development of appropriate specifications/standards.     

Immobilization of α-amylase in vinyl-polymer-based interpenetrating polymer networks

Semi-interpenetrating polymer networks (IPNs) of poly(ethylene glycol), poly(vinyl alcohol) and polyacrylamide were prepared as a support for enzyme immobilization and kinetic studies were performed for the immobilization of -amylase. The effect of IPN composition on the extent of immobilization was investigated and the percentage of relative activity of the immobilized enzyme was evaluated as a function of the chemical architecture of the IPNs, pH and temperature, taking starch as a substrate. The kinetic constants and the maximum reaction velocity were also evaluated. The IPNs were characterized by IR spectral analysis.     

Small-angle X-ray study of air-dried elastoidin using three- and one- dimensional correlation functions obtained from slit-smeared intensity

In the present paper an isotropic sample of air-dried elastoidin has been studied considering it to be a non-ideal two-phase densely packed system after the theories by Vonk [1]. The relevant important physical parameters obtained for the sample areE, the width of the transition layer,D, the average periodicity transverse to the layers, S/V, the specific inner surface ₁ and ₂, the volume fraction of two phases, i. e. matter and void,l ₁ andl ₂ the transversal lengths,l _r, the range of inhomogeneity,l _c, the length of coherence and 2E/D, the volume fraction of the transition layer. The values ofE obtained by two approches as given by Vonk [1] and Ruland [2] show but a small difference indicating the correctness of the analysis.     

Favorskii rearrangement of α,β-epoxy ketones

Reactions of α,β-epoxy ketones with nucleophilic bases generally take one of two courses: (1) α-displacement followed by β-elimination of water or (2) Favorskii rearrangement via a cyclopropanone or zwitterion intermediate. Among the factors that appear to control these reactions, it is suspected that an α′-substituent effect may operate. Such an effect has been confirmed by observing the conversion of 3,5,5,6 - tetramethyl - 2,3 - epoxycyclohexanone (1) to the ring-contracted γ-lactone 3, together with other Favorskii rearrangement products, on treatment with refluxing methanolic potassium hydroxide. The α′-methyl substituted steroid 2 under similar reaction conditions was transformed into roughly equal amounts of 4, 5 and 4 (all rationalized by a Favorskii-like mechanism). In each case the analogous epoxy ketone lacking an α′-Me substituent failed to give any Favorskii products.     

Emulsion copolymerization behavior of α-methylstyrene with methacrylonitrile

The emulsion copolymerization behavior of α-methylstyrene with methacrylonitrile is described. The effects of polymerization temperature, potassium persulfate initiator concentration, sodium lauryl sulfate emulsifier concentration on copolymer yield, molecular weight, and rate of copolymerization are described. The copolymer was found to have an azeotropic composition at 43 mole-% AMS. Reactivity ratios were determined to be 0.06 and 0.28 for AMS and MAN, respectively.     

Mass spectrometric methods for the analysis of chlorinated and nitrated isoflavonoids: a novel class of biological metabolites

Electrospray ionization combined with tandem mass spectrometry was applied to a study of some representative chlorinated and nitrated isoflavones-potential metabolites of isoflavones in inflammatory cells. Upon collision-induced dissociation of deprotonated [M - H](-) ions of these compounds, a number of structurally characteristic product ions were produced. The product ion analysis of 3'- and 8-chlorodaidzein in the tandom mass spectra led to ready differentiation of these isomers. 3-Nitro derivatives of both genistein and daidzein have product ions due to the losses of HNO(2) and two OH groups. Chlorinated derivatives of isoflavones were detected in cell-based experiments and their structures were proposed by comparing the tandem mass spectra of their product ions with those of standards. This work provides a suitable analytical basis to aid the characterization of chlorinated and nitrated metabolites in studies in vivo and in vitro.     

Graphite rod atomization and atomic fluorescence for the simultaneous determination of silver and copper in jet engine oils

S-Methyldithizone(5-methylmercapto-1,5-diphenylformazan) reacts with the chlorides of copper(II), mercury(II) and phenylmercury(II) to give the 1:1 chelates [CuCl(MeDz), HgCl(MeDz) and C₆H₅Hg(MeDz)] and with nickel(II) and palladium(II) to give the 1:2 chelates, M(MeDz)₂. All these complexes are intensely coloured in chloroform solution. No complexes are formed from cobalt(II), manganese(II) or zinc(II) or from the nitrates or acetates of copper and mercury. Coordination increases the reactivity of the sulphur atom in dithizone. Whereas dithizone is unaffected by methyl iodide, nickel dithizonate, Ni(HDz)₂, gives Ni-(MeDz)₂ when heated with methyl iodide in ethanol in the presence of sodium acetate; palladium dithizonate behaves similarly. The 1:1 adduct of nickel dithizonate with 2,2'-bipyridyl gave only Ni(MeDz)₂ on treatment with methyl iodide, and this complex would not form an adduct with bipyridyl. On standing in the light, Ni(MeDz)₂ reacted photochemically to give the yellow isomer of S-methyl-dithizone.     

Reversed-phase ion-pair liquid chromatography of the angiotensins

The isocratic reversed-phase liquid chromatography of the angiotensins and a number of their synthetic analogues is described. Complete separation of 10 out of 12 peptides was achieved through a solvent optimization strategy with a total analysis time of about 20 min. The retention behavior of the angiotensins studied was described in terms of the hydrophobic contribution of their amino acid residues; there was good correlation between predicted and experimental retention for those peptides that were retained by a common mechanism. However, because ion-pair chromatography was required for good peak symmetry, retention was substantially modulated by the presence of acidic and basic residues. The limit of detection of these peptides was 3-5 pmol by UV absorbance at 214 nm. For those peptides containing a primary amino group the detection limit was improved by two orders of magnitude by fluorogenic derivatization with naphthalene-2,3-dicarboxaldehyde/cyanide to the corresponding N-substituted 1-cyanobenz[f]isoindole (CBI) derivatives. The contribution of the CBI ring system to retention was also investigated.     

Synthesis,Characterization and Crystal Structures of new Palladium(II) Complexes and the first Platinum(III) Complex Containing ATT (ATT = 6‐Aza‐2‐thiothymine)

Treatment of the ligand 6‐aza‐2‐thiothymine (ATT, HL, 1 ) with palladium chloride in methanol forms the ionic complex [(HL)₄Pd]Cl₂·8MeOH ( 2 ), while its reaction with palladium iodide in same solvent produces the neutral complex trans‐[(HL)₂PdI₂]·2MeOH ( 3 ) in high yields. The reaction of 1 with Na₂[PdCl₄] in the presence of sodium acetate in a molar ratio of 2:1:2 and with platinum(II) chloride in presence of sodium acetate led to the dimer tetranuclear complexes [(L₄Pd₂)NaCl]₂·8MeOH ( 4 ) and [L₄Pt₂Cl₂]·6MeOH·H₂O ( 5 ). The latter is the first Pt^III complex of the ligand. All complexes were characterized by elemental analyses and IR spectroscopy and the crystal structures of 2 , 3 , 4 and 5 are determined by single‐crystal X‐ray diffraction. Crystal data for 2 at ?80 °C: triclinic space group , a = 1006.6(1), b = 1006.9(1), c = 1158.1(1) pm, α = 85.20(1)°, β = 83.84(1)°, γ = 88.91(1)°, Z = 1, R₁ = 0.0278; for 3 at ?80 °C: triclinic space group , a = 490.5(1), b = 977.2(2), c = 1116.8(2) pm, α = 90.26(1)°, β = 102.33(1)°, γ = 96.08(1)°, Z = 1, R₁ = 0.0394; for 4 at ?80 °C: orthorhombic space group Ccca, a = 1791.7(2), b = 1874.1(2), c = 2044.0(1) pm, Z = 4, R₁ = 0.0341 and for 5 at ?80 °C: monoclinic space group P2₁/c, a = 1464.3(1), b = 2003.7(1), c = 1368.5(1) pm, β = 95.66(1)°, Z = 4, R₁ = 0.0429.