[Show abstract][Hide abstract] ABSTRACT: Monitoring of low-molecular-weight aldehyde levels in excipients used in liquid/semi-solid based capsule (LFC) dosage forms plays a critical role in the development of these pharmaceutical products. A simple, sensitive and specific method based on gas chromatography coupled with mass spectrometry (GC-MS) utilizing an Rtx-5MS capillary column was developed and validated for the detection and quantification of C1-C8 aliphatic aldehydes in LFC excipients at sub-microg/g levels. The proposed procedure is based on the derivatization of aldehydes in 10:1 (v/v) acetonitrile:water with O-2,3,4,5,6-(pentafluorobenzyl) hydroxylamine hydrochloride (PFBHA), followed by direct GC analysis of aldehyde-PFBHA-oxime derivatives with negative chemical ionization (NCI) MS detection. The method developed was successfully applied to the analysis of short chain aldehydes in 30 typical LFC excipients. An example case study on the formation and growth of aldehydes in these excipients under accelerated storage conditions is also reported.
Journal of Chromatography A 09/2007; 1160(1-2):299-305. DOI:10.1016/j.chroma.2007.05.095 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Medium chain length (C8, C10) mono-, di- and triacylglycerols (MCGs) are used in pharmaceutical formulation development of poorly soluble compounds, as a means to increase their oral bioavailability. The ratios of C8 and C10 fatty acid components along with the ratio of monoglycerides, diglycerides and triglycerides can significantly impact overall solubilizing characteristics both in vitro and in vivo. Existing literature methods either do not have the desired selectivity or simplicity to adequately characterize these MCGs. A reversed-phase HPLC method has been developed utilizing a Waters Symmetry C18 (150 mm x 4.6 mm, 3.5 microm particle size) column with a gradient of acetonitrile and water. The effluent was monitored using a UV detector at 220 nm and relative response factors were determined for all components with available standards to allow for accurate quantitation. The RP-HPLC method was optimized for selectivity, sensitivity and efficiency and was successfully applied to the characterization of commercial samples yielding superior sensitivity and ease of preparation compared to existing compendial methods.
Journal of Pharmaceutical and Biomedical Analysis 04/2006; 40(4):896-900. DOI:10.1016/j.jpba.2005.08.024 · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The adverse effect of reactive chemical residues on the quality of drug products has necessitated the determination of low-molecular-weight aldehydes in pharmaceutical excipients. An analytical methodology for the detection of trace amounts of C1-C8 aliphatic aldehydes and benzaldehyde in excipients is described. The proposed procedure is based on the derivatization of aldehydes in aqueous solution with O-2,3,4,5,6-(pentafluorobenzyl) hydroxylamine hydrochloride (PFBHA), followed by static headspace gas chromatographic (SHS-GC) analysis of PFBHA aldehyde oximes with negative chemical ionization (NCI) MS detection. The method developed was demonstrated to be simple, selective, sensitive, and was successfully applied to the screening of aldehydes at sub-microg/g levels in over 30 typical excipients. The most abundant aldehydes found in the samples were formaldehyde and acetaldehyde, for which a rapid and reliable routine quantification method by readily available SHS-GC instrumentation coupled with flame-ionization detection was also developed and validated.
Journal of Chromatography A 03/2006; 1104(1-2):1-10. DOI:10.1016/j.chroma.2005.10.084 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of dissolved gases on the performance of aqueous dissolution media have been studied exten- sively, but little has been published regarding the effect of dissolved gases on surfactant containing dissolu- tion media. There are various methods available to control the level of dissolved gases in surfactant media, but regardless of the method used or level of dissolved gases achieved, the media will equilibrate to atmos- pheric conditions within approximately one hour. Therefore, elaborate techniques to control the level of dissolved gases are unnecessary, and the variability associated with dissolved gases can be minimized by performing the dissolution experiment at equilibrium.
[Show abstract][Hide abstract] ABSTRACT: A systematic approach for the identification and quantification of organic volatile impurities (OVIs) in pharmaceutical excipients is described. Analytical procedures utilizing static headspace capillary gas chromatography coupled with flame-ionization and MS detection techniques were developed for the analysis of toxic ICH class 1 solvents and US Pharmacopeia OVIs at sub-ppm levels, and commonly used organic solvents in a wide range of concentrations. Chromatographic conditions and headspace parameters for the methods were optimized for separation, sensitivity, and speed. The proposed methodologies were demonstrated to be selective, accurate, and reproducible, and were successfully applied to the rapid screening of OVIs in typical excipients.
Journal of Chromatography A 03/2004; 1027(1-2):83-91. DOI:10.1016/j.chroma.2003.08.086 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A rapid static headspace-gas chromatographic (SHS-GC) method was developed and validated for the quantitation of residual solvents in pharmaceutical gel extrusion module (GEM) tablet formulations. A static headspace sampling technique was utilized to overcome the difficulties imposed by direct injection methods. A Rtx-1701 megabore capillary column was selected to achieve optimal resolution among organic volatile chemicals used commonly in the manufacturing of GEM tablets, residual solvents in the active ingredient and excipients, and other formulation matrix artifacts. A 50-mM pH 3.0 sodium phosphate buffer was used as a sample diluent to minimize matrix effects. The instrumental parameters of the SHS-GC method were optimized for sensitivity and precision. Quantitation was performed by external standard analysis. The SHS-GC method was validated according to regulatory requirements and produced acceptable results with respect to specificity, linearity, range, detection and quantitation limits, precision, and accuracy.
Journal of Pharmaceutical and Biomedical Analysis 06/2002; 28(3-4):673-82. DOI:10.1016/S0731-7085(01)00657-4 · 2.98 Impact Factor