An examination of the thermodynamics of fusion, vaporization, and sublimation of ibuprofen and naproxen by correlation gas chromatography

The vaporization enthalpies of (S)-ibuprofen and (S)-naproxen measured by correlation gas chromatography at T = 298.15 K are reported and compared with literature values. Adjustment of the fusion enthalpies of (RS)- and (S)-ibuprofen and (S)-naproxen to T = 298.15 K and combined with the vaporization enthalpy of the (S)-enantiomer of both ibuprofen and naproxen also at T = 298.15 K resulted in the sublimation enthalpies of both (S)-enantiomers. On the assumption that the vaporization enthalpy of the racemic form of ibuprofen is within the experimental uncertainty of the chiral form, the sublimation enthalpy of racemic ibuprofen was also evaluated. The vaporization and sublimation enthalpies compare favorably to the most of the literature values for the racemic form of ibuprofen but differ from the value reported for chiral ibuprofen. The literature values of (S)-naproxen are somewhat smaller than the values measured in this work. The following vaporization enthalpies were measured for (S)-ibuprofen and (S)-naproxen, respectively: ΔH(vap) (298.15 K), 106.0 ± 5.5, 132.2 ± 5.0 kJ·mol(-1) . Sublimation enthalpies of 122.7 ± 5.6 and 155.2 ± 7.1 kJ·mol(-1) were calculated for the (S)-enantiomers of ibuprofen and naproxen and a value of 128.9 ± 5.8 kJ·mol(-1) was estimated for the racemic form of ibuprofen.     

An examination of the thermodynamics of fusion, vaporization, and sublimation of (R,S)- and (R)-flurbiprofen by correlation gas chromatography

The vaporization, fusion, and sublimation enthalpies of (R,S)- and (R)-flurbiprofen at T = 298.15 K are reported and compared with literature values when available. Correlation gas chromatography experiments were first performed to identify appropriate standards that could be used for materials containing a single fluorine substituent. Subsequent correlations resulted in a vaporization enthalpy for (R,S)-flurbiprofen and (R)-flurbiprofen, ΔH(vap) (298.15 K), of (127.5 ± 5.5) and (127.4 ± 4.7) kJ mol, respectively. Fusion enthalpies, ΔH(fus) (387 K), of (28.2 ± and, ΔH(fus) (381 K), (22.8 ± kJ mol(-1) were also measured by differential scanning calorimetry for the racemic and chiral forms of flurbiprofen. Adjusted to T = 298.15 K and combined with the vaporization enthalpy resulted in sublimation enthalpies, ΔH(sub) (298.15 K), of (155.6 ± 5.8) and (145.1 ± 5.7) kJ mol(-1) for (R,S)- and (R)-flurbiprofen, respectively. The fusion enthalpy measured for the racemic form was in excellent agreement with the literature value, while the sublimation enthalpy varies substantially from previous work. Two weak solid-solid phase transitions were also observed for (R)-flurbiprofen at T = 353.9 K (0.30 ± 0.1) and 363.2 K (0.21 ± 0.03) kJ · mol(-1).     

Thermodynamics of solubility, sublimation and solvation processes of parabens.

Saturated vapor pressures for a number of parabens (methyl- (MePB); ethyl- (EtPB), n-propyl- (PrPB) and n-butyl- (BuPB)) were obtained and from their respective temperature dependences the sublimation enthalpy, DeltaH(sub)( degrees ), and sublimation entropy, DeltaS(sub)(degrees), as well as their respective relative fractions in the process calculated. The sublimation enthalpies are: DeltaH(sub)(degrees)(MePB)=98.8+/-0.8; DeltaH(sub)(degrees)(EtPB)=100.9+/-0.7; DeltaH(sub)(degrees)(PrPB)=123.7+/-0.6; DeltaH(sub)(degrees)(BuPB)=108.4+/-0.8 kJmol(-1). The obtained values are discussed with regard to X-ray data from the literature. Theoretical calculations of the respective crystal lattice energies were carried out and compared to the experimental data. The following parameters were analyzed: (a) energetic contribution of van der Waals forces and hydrogen bonding to the total packing energy of the crystals; (b) contributions of the different fragments of the paraben molecules to the packing energy; (c) influence of bias of the supposed C-H distances on the result of the calculation procedure. Enthalpies of evaporation were estimated from the measured enthalpies of sublimation and enthalpies of fusion, and compared with literature data. Moreover, the thermodynamic functions of solvation of the molecules in water and in a number of n-alcohols were evaluated. The thermodynamic terms (Gibbs energy, enthalpy and entropy) of the solvation process were split up in their respective specific and nonspecific fraction, and these values compared for all combinations of parabens and solvents. The influence of mutual saturation of the phases in the water-octanol system on the partitioning process of the molecules is also discussed.     

Determination of cisapride, its oxidation product, propyl and butyl parabens in pharmaceutical dosage form by reversed-phase liquid chromatography

A simple, rapid and reproducible high-performance liquid chromatography (HPLC) assay for cisapride, its oxidation product (OP), propyl and butyl parabens in a pharmaceutical formulation is described. Chromatography was performed at room temperature by pumping acetonitrile–20 mM phosphate buffer pH 7 (50:50, v/v) at 1.5 ml min⁻¹ through C₈ reversed-phase column. Cisapride, OP, propyl and butyl parabens were detected at 276 nm and were eluted at 9.7, 3.1, 5.1 and 7.1 min, respectively. Calibration plots were linear (r>0.999) for all compounds from 0.5 to 200 μg ml⁻¹ for cisapride and OP and 0.1–200 μg ml⁻¹ for propyl and butyl parabens. Detection limits for cisapride, OP, propyl and butyl parabens were 40, 46, 48 and 54 ng ml⁻¹, respectively. Forced degradation investigations showed that cisapride does not undergo degradation under heat, acidic and basic conditions but it was susceptible to oxidation. The proposed method was successfully applied to the assay of cisapride in the presence of preservatives and OP in a commercial suspension.     

An uncertainty budget for the measurement of ethanol in blood by headspace gas chromatography

An uncertainty budget was constructed for the measurement of ethanol in blood by headspace gas chromatography. The uncertainty budget, covering the analytical range of ethanol concentrations up to 3.00 g/kg, included analytical uncertainty components, traceability uncertainty components, and effects caused by interindividual variation in blood water content. The analytical combined standard uncertainty was estimated from duplicate measurements of real samples and included contributions from headspace recovery, variation between columns, injection, repeatability of analytical signals, and statistical uncertainty of the calibration function. The traceability uncertainty was estimated in a sub-budget based on information about the calibrator and about the preparation of the aqueous standards. Two uncertainty components depended on the interindividual variation in blood water content. First, it caused uncertainty on the density of the blood, and second, it had an effect on the gas phase concentration of ethanol when doing the headspace sampling. These effects as well as their covariance were included in the uncertainty budget. For fresh blood samples, the analytical uncertainty was the dominating uncertainty component, accounting for approximately 90% of the variance. For blood samples collected 100 h postmortem, the interindividual variation in blood water content was the largest uncertainty component. It was demonstrated that subtracting a "safety margin" of 0.1 g/kg from the results was sufficient to keep the risk of committing a type 1 error below 0.1% in ethanol concentrations ranging up to 2 g/kg for fresh blood samples. This risk was higher for postmortem blood samples because of the higher uncertainty of measurement, but still less than approximately 1.4%.     

Analysis of diethylcarbamazine and diethylcarbamazine-N-oxide by gas chromatography

Diethylcarbamazine (DEC, 1-diethylcarbamyl-4-methylpiperazine) is an antiparasitic piperazine derivative used in the treatment of lymphatic filariasis caused byWuchereria bancrofti, Brugia malayi orBrugia timori. DEC-N-oxide is a major metabolite in humans and has antifilarial activity. In carrying out pharmacokinetic studies, gas chromatographic analysis of DEC in plasma can be complicated by the presence of the metabolite, since the thermally unstable DEC-N-oxide is converted back to a material which coelutes with DEC under the conditions of the analysis. We now report a method to separate DEC-N-oxide from DEC in plasma using solid phase extraction with subsequent gas chromatographic analysis using a nitrogen specific detector. One-diethylcarbamyl-4-ethylpiperazine (E-DEC) was the internal standard. The standard curve of DEC was linear in the range of 10 to 200 ng/ml as described by Y=0.0350+0.0128X, R²=0.999. The limit of quantitation was 4 ng/mL. Reproducibility at 10, 100 and 200 ng/mL concentration points of the standard curve gave coefficient variations of 6.1%, 7.8% and 1.6%, respectively. The recovery following solid phase extraction was 99.3% for DEC and 94.8% for the internal standard. This sensitive and specific analytical method is suitable for pharmacokinetic studies of DEC.     

Detection of ritalinic acid in urine by thin-layer chromatography and gas chromatography

A new method for the analysis of ritalinic acid, the major metabolite of methylphenidate in urine, is described. The procedure involves solid-phase extraction of ritalinic acid from urine using C-18 reverse phase columns. The ritalinic acid is methylated to form methylphenidate which, together with an internal standard, is then extracted into chloroform and analyzed by gas chromatography using a flame ionization detector. This procedure gives essentially quantitative recovery of ritalinic acid from 10 mL urine and is linear in the range of 0 to 10 micrograms/mL. A positive analysis for ritalinic acid is confirmed by thin-layer chromatography. Detection sensitivities of greater than or equal to 1 micrograms/mL urine were observed for both procedures.     

Determination of benzalkonium chloride by gas chromatography

A new, simple, and useful approach for the analysis of benzalkonium chloride is presented. A gas chromatography (GC) has been used to pyrolyze benzalkonium chloride in a specific and reproducible manner to yield two tertiary amines for each homologue of benzalkonium chloride present. These are separated by GC and are used to determine the homologue composition of the benzalkonium chloride. These determinations can be made with an analysis time of 25 min/sample.     

Quantitative analysis of dimethyl titanocene by iodometric titration, gas chromatography and NMR

In this study we report the use of an automated iodometric titration method and a novel gas chromatography (GC) method for the quantitative analysis of dimethyl titanocene (DMT), a key raw material in drug synthesis. Both approaches are based on the reaction of DMT in toluene or tetrahydrofuran solutions with iodine. In the case of iodometric titration, excess iodine is titrated with a standardized aqueous sodium thiosulfate solution to a potentiometric end-point for the determination of DMT concentration. Alternatively, GC is employed to measure the concentration of iodomethane, a product of the reaction between DMT and iodine, in order to determine the concentration of DMT in the solution. Excellent agreement between iodometric titration, GC and NMR results using several DMT samples confirms the accuracy of the two methods and strongly supports the use of either method as a replacement to the expensive NMR for quantitative DMT analysis. The relatively few sources of error associated with the two methods, their ubiquitous nature and ease of application in routine analysis make them the analytical methods of choice, among all. Both methods have been validated according to ICH requirements. The use of iodometric titration method for DMT analysis is demonstrated with a couple of applications.     

气相色谱法测定脂肪酶的活力

本文发展了一种以气相色谱检测脂肪酶活力的方法。以三丁酸甘油酯为底物,通过气相色谱对产物正丁酸进行定性定量分析。正丁酸在0.11～11.35 mmol·L^-1内线性关系良好, 回归方程为: y = 45 464x - 3 115.2, r = 0.996 8。反应时间仅需5 min,最适pH值和温度分别为7.5和32 ℃。低、中、高3个浓度正丁酸的回收率分别为90.3%,104.6%和89.4%;RSD分别为3.01%,4.50%和6.64%。通过实验测定出K_m =0.25 mmol·mL^-1,奥利司他的半数抑制浓度 (IC₅₀) 为0.048 5 mg·mL^-1。本方法具有反应体积小、操作简单、快速、灵敏等特点。     

Determination of phenolalkylamines, narcotic analgesics, and beta-blockers by gas chromatography/mass spectrometry

An analytical procedure for determination of phenolalkylamines, narcotic analgesics, and beta-blockers in urine by gas chromatography/mass spectrometry (GC/MS) is described. The detection of phenolalkylamines, narcotic analgesics, and beta-blockers is based on acid hydrolysis, liquid-liquid extraction, and selective derivatization. For screening of phenolalkylamines the m/e 179 and 267 ions were monitored by GC/MS. With narcotic analgesics, the extracted ion corresponded to the molecular ion (M+) of the drug and two additional characteristic ions. Beta-blockers were analyzed as the selectively derivatized forms of the parent molecule and its metabolites by GC/MS with selected ion monitoring. The ions monitored for screening of beta-blockers containing an isopropylamine group were m/e 284 and 129 ions. The ion at m/e 86 was monitored to characterize the tert-butylamine group of beta-blockers.     

Simultaneous determination of glutethimide,methyprylon, and methaqualone in serum by gas liquid chromatography

A gas chromatographic method is described that permits the simultaneous determination of glutethimide, methyprylon, and methaqualone in serum samples. The threshold of sensitivity for each of the three hypnotics is 0.2 mg/l.