HPLC Method for the Simultaneous Determination of the UV-Filters Butyl Methoxy Dibenzoylmethane and Octocrylene in the Presence of Their Photodegradants

Butyl methoxy dibenzoylmethane (BMDM) and octocrylene (OC), common UV-filters in sunscreen products are often used in combination. Together they provide broad spectrum photoprotection from exposure to both UVA- and UVB-light. These UV-filters may, however, undergo photodegradation and generate photodegradants, resulting in a potential loss of photoprotection. It is thus a concern that the photostability testing as described by the ICH Guideline Q1B is not a requirement for sunscreen products in Australia, Europe or the USA. UV-filter photodegradants have in addition been shown to be toxic, highlighting the importance of their separation from the parent UV-filters. An HPLC method was developed and validated to quantitatively determine a combination of these UV-filters in the presence of their photodegradants. Reverse-phase chromatography was employed, using a C18 column and an isocratic mobile phase consisting of methanol/water/acetic acid (89/10/1 v/v). Validation according to the ICH guidelines for linearity, accuracy, precision, sensitivity, specificity and robustness was confirmed. The developed and validated method was then successfully applied to the determination of BMDM and OC in an aqueous cream base, typically used in sunscreens, after photostability testing, according to the ICH Guideline Q1B. In addition, the diketo-enol ratio of BMDM in methanol-d ₄ was determined by NMR and the two major photodegradants were identified by FTMS and LC–MS.

     

HPLC Method for the Simultaneous Determination of the UV-Filters Butyl Methoxy Dibenzoylmethane and Octocrylene in the Presence of Their Photodegradants

Butyl methoxy dibenzoylmethane (BMDM) and octocrylene (OC), common UV-filters in sunscreen products are often used in combination. Together they provide broad spectrum photoprotection from exposure to both UVA- and UVB-light. These UV-filters may, however, undergo photodegradation and generate photodegradants, resulting in a potential loss of photoprotection. It is thus a concern that the photostability testing as described by the ICH Guideline Q1B is not a requirement for sunscreen products in Australia, Europe or the USA. UV-filter photodegradants have in addition been shown to be toxic, highlighting the importance of their separation from the parent UV-filters. An HPLC method was developed and validated to quantitatively determine a combination of these UV-filters in the presence of their photodegradants. Reverse-phase chromatography was employed, using a C18 column and an isocratic mobile phase consisting of methanol/water/acetic acid (89/10/1 v/v). Validation according to the ICH guidelines for linearity, accuracy, precision, sensitivity, specificity and robustness was confirmed. The developed and validated method was then successfully applied to the determination of BMDM and OC in an aqueous cream base, typically used in sunscreens, after photostability testing, according to the ICH Guideline Q1B. In addition, the diketo-enol ratio of BMDM in methanol-d ₄ was determined by NMR and the two major photodegradants were identified by FTMS and LC–MS.     

Characterising the geometric diversity of functional groups in chemical databases

Summary We have developed a program, HookSpace, which provides a simplistic approach to assessing the diversity of molecular databases. The spatial relationship between pairs of intramolecular functional groups can be analysed in a variety of ways to provide both qualitative and quantitative measures of diversity. Results are described and contrasted for two commercially available databases and a combinatorial library of benzodiazepam derivatives. HookSpace highlights the main differences in molecular content of these data sets.     

Characterization of inositol phosphorylceramides from <Emphasis Type="Italic">Leishmania major</Emphasis> by tandem mass spectrometry with electrospray ionization

We describe tandem mass spectrometric approaches, including multiple stage ion-trap and source collisionally activated dissociation (CAD) tandem mass spectrometry with electrospray ionization (ESI) to characterize inositol phosphorylceramide (IPC) species seen as [M - H](-) and [M - 2H + Li](-) ions in the negative-ion mode as well as [M + H](+), [M + Li](+), and [M - H + 2Li](+) ions in the positive-ion mode. Following CAD in an ion-trap or a triple-stage quadrupole instrument, the [M - H](-) ions of IPC yielded fragment ions reflecting only the inositol and the fatty acyl substituent of the molecule. In contrast, the mass spectra from MS(3) of [M - H - Inositol](-) ions contained abundant ions that are readily applicable for assignment of the fatty acid and long-chain base (LCB) moieties. Both the product-ion spectra from MS(2) and MS(3) of the [M - 2H + Alk](-), [M + H](+), [M + Alk](+), and [M - H + 2Alk](+) ions also contained rich fragment ions informative for unambiguous assignment of the fatty acyl substituent and the LCB. However, the sensitivity of the ions observed in the forms of [M - 2H + Alk](-), [M + H](+), [M + Alk](+), and [M - H + 2Alk](+) (Alk = Li, Na) is nearly 10 times less than that observed in the [M - H](-) form. In addition to the major fragmentation pathways leading to elimination of the inositol or inositol monophosphate moiety, several structurally informative ions resulting from rearrangement processes were observed. The fragmentation processes are similar to those previously reported for ceramides. While the tandem mass spectrometric approach using MS(n) (n = 2, 3) permits the structures of the Leishmania major IPCs consisting of two isomeric structures to be unveiled in detail, tandem mass spectra from constant neutral loss scans may provide a simple method for detecting IPC in mixtures.     

Simple Zeros of the Riemann Zeta-Function

Assuming the Riemann Hypothesis, Montgomery showed by meansof his pair correlation method that at least two-thirds of thezeros of Riemann's zeta-function are simple. Later he and Taylorimproved this to 67.25 percent and, more recently, Cheer andGoldston increased the percentage to 67.2753. Here we proveby a new method that if the Riemann and Generalized LindelöofHypotheses hold, then at least 70.3704 percent of the zerosare simple and at least 84.5679 percent are distinct. Our methoduses mean value estimates for various functions defined by Dirichletseries sampled at the zeros of the Riemann zeta-function. 1991Mathematics Subject Classification: 11M26.     

Quantum Zeno and anti-Zeno paradoxes

Continuous observation of a time independent projection operator is known to prevent change of state (the quantum Zeno paradox). We discuss the recent result that generic continuous measurement of time dependent projection operators will in fact ensure change of state: an anti-Zeno paradox.     

粉粒体两相流的电容层析成象测量

粉粒体系统中的固相浓度分布的在线测量是十分困难的问题．电容层析成象技术是一种近年来发展起来的非侵入式快速浓度场测量技术．它不干扰流场，不受流动中颗粒浓度、加速度、不透明等因素的制约．本文讨论其测量原理、应用、近期进展、存在的主要问题及其解决的对策．