Unknown residual solvents identification in drug products by headspace solid phase microextraction gas chromatography-mass spectrometry

Summary A sensitive headspace SPME method for the extraction of residual solvents from pharmaceutical products has been developed and optimized. It was found that minimizing sample and headspace volume has a beneficial effect on extraction efficiency. At the same time the method reproducibility was seriously affected by reducing sample and headspace volume. The added air volume was not found to have any significant influence on method sensitivity. The method showed reproducibilities of less than 10% and detection limits as low as 1 ppb for benzene and dichloromethane. The headspace SPME method is around 1000 times more sensitive than static headspace. The optimized parameters were headspace volume 1.5 mL, sample volume 10 μL, and extraction time 30 min. The method was successfully applied to the identification of unknown residual solvents in three different proprietary active drug substances and was successfully applied to the confirmation of the presence of benzene in a proprietary drug substance. Presented at Balaton Symposium '01 on High-Performance Separation Methods, Siófok, Hungary, September 2–4, 2001     

Synthesis and magnetic properties of copper (II)-lanthanoid (III) binuclear complexes with N,N′-bis(3-aminopropyl) oxamido ligand

Six novel μ-oxamido binuclear complexes, namely Cu(axpn)Ln(L)₂(ClO₄)₃ (Ln: Eu, Gd, Tb, Nd, Ho, Er), where oxpn is N,N'-bis(3-aminopropyl) oxamido, L denotes 5-nitro,10-phenanthroline (abbreviated as NO₂-phen), have been synthesized and characterised. The magnetic susceptibility of complexes Cu(oxpn)Gd(NO₂-phen)2(ClO₄)₃.2H₂O was measured over the 4–300 K and the observed data were successfully simulated by equation based on spin Hamiltonian operator (H = -2J₁ · S₂), giving the exchange integral J(Cu-Gd)=-1.62 cm^?1. This indicates a weak antiferromagnetic interaction between the Cu(II) and Gd(III) ions.     

Crystal Structures and Magnetic Properties of the Two Misfit Layer Compounds: [SrGd0.5S1.5]1.16 NbS2 and [Sr(Fe,Nb)0.5S1.5]1.13 NbS2

Crystal structures of two new misfit compounds, [SrGd_0.5S_1.5]_1.16NbS₂ and [Sr(Fe,Nb)_0.5S_1.5]_1.13NbS₂, were determined through the composite approach, i.e., by refining each subpart (Q, H-parts, and the common part) of these composite materials, separately. The Q-part is a three-atom-thick layer, with the NaCl-type structure, where external SrS planes enclose the inner GdS or (Fe,Nb)S plane; the structural difference between these two compounds lies in the central layer within the Q-part: Gd and S atoms are in special positions (octahedral coordination), while Fe and S atoms are statistically distributed on split (×4) positions (tetrahedral coordination) around a central unique site (=special position occupied by Nb). The H-part is a sandwich of sulfur planes enclosing the inner Nb plane as observed for the structure of the binary compound NbS₂ itself. The Sr-Gd derivative shows a paramagnetic behavior in the whole studied temperature range (2-300 K). On the other hand, antiferromagnetic interactions occur in the Sr-Fe derivative; the complex magnetic behavior of this compound is related to the statistical distribution of Fe atoms which leads to frustration of the magnetic interactions. At room temperature, experimental values obtained from Mössbauer spectrum correspond to Fe³⁺ in tetrahedral sulfur environment: isomer shift δ=0.32 mm s⁻¹, and quadrupole splitting ΔE=0.48 mm s⁻¹.     

三核苯甲酸铁配合物[Fe3O(OBZ)6(H2O)3](NO3)(acetone)5(OBZ-=苯甲酸根)的结构和磁性

合成了三核苯甲酸铁配合物［Ｆｅ３Ｏ（ＯＢＺ）６（Ｈ２Ｏ）３］（ＮＯ３）（ａｃｅｔｏｎｅ）５。测定了其晶体结构，其中三个铁形成等边三角形结构。配合物的变温磁化率表明，分子内三个铁之间有弱的反应磁性交换作用，Ｊ＝－３３．１８ｃｍ＾－１。分子之间则有更弱的反铁磁性交换作用，ＺＪ＾＇＝－１．１４ｃｍ＾－１。     

Synthesis,crystal structure and magnetic properties of a novel manganese(II)-nitronyl nitroxide-azido(μ<Subscript>1,1</Subscript> and μ<Subscript>1,3</Subscript>) one-dimensional complex

A novel one-dimensional manganese(II) complex containing nitronyl nitroxide radical [Mn₂(IM2-py)₂(Ac)₂(μ_1,1-N₃)(μ_1,3-N₃) · EtOH] _n was synthesized and characterized structurally and magnetically. It crystallizes in the monoclinic space group p2₁/n. Each Mn(II) ion is six-coordinated in a distorted octahedral environment. The two N atoms of the nitronyl nitroxide radical and the two O atoms of acetate ligands are in the equatorial plane, whereas the two different azido bridging ligands are in trans axial position. Mn(II) ions are linked by nitrogen atom of μ_1,1-azido and oxygen atoms of two carboxy groups to form a Mn-Mn unit. Mn-Mn units are linked by azido ligands through μ_1,3 bridging style to form a one-dimensional chain. The compound is connected by the coordination bonds, π-π interactions and hydrogen bonds as a three-dimensional structure. Magnetic susceptibility data support that there are stronger antiferromagnetic interactions between the radical and Mn(II) ion, weak antiferromagnetic interactions between the Mn-R units, and very weak antiferromagnetic interactions between the R-Mn-Mn-R units.     

毛细管气相色谱法测定兰索拉唑中有机溶剂残留量

以N,N-二甲基甲酰胺(DMF)为溶剂,丁酮为内标,采用PV-101毛细管色谱柱 (30 m×0．22 mm),氢火焰离子化检测器,建立兰索拉唑中五种有机溶剂甲醇、乙醇、丙酮、二氯甲烷、乙酸乙酯残留量的定量分析方法。五种有机溶剂检出限分别为0．002 4％,0．002 4％, 0．001 2％,0．000 6％,0．000 6％;在10-1000 mg·L-1浓度范围内,各组分线性关系良好;对应的平均回收率分别为100．8％±3．6％,102．1％±2．3％,99．97％±4．1％,99．63％±2．7％, 102．3％±3．5％。     

Application of Liquid Crystalline NMR Solvents to a Mixture of Ketones

A series of dilute liquid crystalline solvents are used to study the effect of slight anisotropy caused by partial alignment on chemical shift and residual dipolar coupling (RDC) in small molecules. The residual dipolar couplings between protons in solutes are found to be almost independent of the local environment. It is also found that the chemical shift does not change over the concentration range observed. A linear relationship between residual dipolar coupling and liquid crystal concentration is observed at relatively low concentrations, but is severely violated at high concentrations.     

Localized Orbitals vs. Pseudopotential-Plane Waves Basis Sets: Performances and Accuracy for Molecular Magnetic Systems

 Density functional theory, in combination with a) a careful choice of the exchange-correlation part of the total energy and b) localized basis sets for the electronic orbitals, has become the method of choice for calculating the exchange-couplings in magnetic molecular complexes. Orbital expansion on plane waves can be seen as an alternative basis set especially suited to allow optimization of newly synthesized materials of unknown geometries. However, little is known on the predictive power of this scheme to yield quantitative values for exchange coupling constants J as small as a few hundredths of eV (50–300 cm⁻¹). We have used density functional theory and a plane waves basis set to calculate the exchange couplings J of three homodinuclear Cu-based molecular complexes with experimental values ranging from +40 cm⁻¹ to −300 cm⁻¹. The plane waves basis set proves as accurate as the localized basis set, thereby suggesting that this approach can be reliably employed to predict and rationalize the magnetic properties of molecular-based materials. Corresponding author. E-mail: Carlo.Massobrio@ipcms.u-strasbg.fr Received August 5, 2002; accepted August 9, 2002     

Synthesis, X-ray structure and properties of a new nitrite-bound copper(II) complex with 2-(3,5- dimethylpyrazol-1-ylmethyl)pyridine in a CuN4(O) coordination

Synthesis and characterization of a nitrite-bound copper(II) compound [CuL⁴)₂(ONO)]ClO₄ have been achieved (L⁴ = 2-(3,5-dimethylpyrazol-1-ylmethyl)pyridine]. The bidentate ligand L⁴ provides a pyridine and a pyrazole donor site; however, they are separated by a methylene spacer. The complex has been structurally characterized and it belongs to only a handful of complexes having nitrito-bound mononuclear copper(II) centre. The metal atom has a distorted square pyramidal geometry with the copper atom displaced from the equatorial plane by 0.25 Å. In MeCN solution the green complex exhibits a broad ligand-field transition at 655 nm with a shoulder at 675 nm and in dichloromethane-toluene glass (80 K) it exhibits an EPR spectral feature characteristic of the unpaired electron in the d_x²−y² orbital. Variable-temperature (80–300 K) magnetic susceptibility measurements in the solid state as well as room temperature measurement in MeCN solution reveal mononuclear magnetically dilute copper(II) centre. When examined by cyclic voltammetry (MeCN solution) it displays electrochemically irreversible Cu^II---Cu^I response [cathodic peak potential, E_pc (V vs saturated calomel electrode (SCE)): −0.32]. An oxidative response is observed at 1.14 V, probably due to bound-nitrite oxidation and is partially removed to generate a solvated complex at the electrode surface. The latter species gives rise to reversible Cu^II---Cu^I redox response [ ].     

顶空气相色谱法测定卷烟包装材料中的溶剂残留

采用顶空气相色谱法对卷烟包装材料中溶剂残留(乙酸乙酯、乙酸丁酯、甲苯、乙苯等)进行分析,并讨论了各种条件对测定的影响。分析结果表明,该方法对上述4种溶剂残留的检出限范围分别为乙酸乙酯0.4~120 mg.L-1,甲苯0.4~120 mg.L-1,乙酸丁酯1.2~600 mg.L-1,乙苯0.5~150 mg.L-1,测定结果的相对标准偏差为2.5%~3.1%,样品的回收率为90%~95%;方法用于卷烟包装材料实样中溶剂残留的分析。