Validated LC–ESI–MS/MS method for the determination of tunicamycin in rat plasma: Application to a pharmacokinetic study

A liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the quantification of tunicamycin in rat plasma as per regulatory guideline. Chromatography of tunicamycin and the IS in the processed plasma samples was achieved on an X‐Terra phenyl column using a binary gradient (mobile phase A, acetonitrile and mobile phase B, 5 mm ammonium formate) elution at a flow rate of 0.6 ml/min. LC–MS/MS was operated under the multiple reaction monitoring mode using the electrospray ionization technique in positive ion mode and the transitions of m/z 817.18 → 596.10, 831.43 → 610.10, 845.29 → 624.10, 859.23 → 638.10 and 309.24 → 163.20 were used to quantitate homologs A–D and the IS, respectively. The total chromatographic run time was 4.5 min. The correlation coefficient (r²) was >0.99 for all homologs with accuracy 90.7–107.4% and precision 0.74–15.1%. The recovery of homologs was 78.6–90.2%. No carryover was observed and the matrix effect was minimal. Tunicamycin four homologs were found to be stable on the bench‐top for 6 h, for up to three freeze–thaw cycles, in the injector for 24 h and for 1 month at ?80 ° C. The applicability of the validated method has been demonstrated in a rat pharmacokinetic study.     

A Facile One‐Pot Synthesis of 3,5‐Disubstituted Isoxazole Derivatives Using Hydroxy (Tosyloxy) Iodobenzene

Hydroxy (tosyloxy) iodobenzene (HTIB), a hypervalent iodine reagent, has been extensively used for oxidative transformations. We have developed a one‐pot synthesis wherein aldoximes when reacted with alkynes in the presence of HTIB result in the direct formation of isoxazoles. This simple and straightforward reaction allows for ease of purification while leading to the formation of high purity 3,5‐disubstituted isoxazoles in moderate yields.     

Microwave Activated Solid Support Synthesis of New Antibacterial Quinolones

Summary.  A novel synthesis of 6-fluoro-7-(5-aryl-1,3,4-thiadiazol/oxadiazol-2-yl-sulfanyl)-4-quinolone-3-carboxylic acids from 7-chloro-6-fluoro-4-quinolone-3-carboxylic acid and 5-substituted 1,3,4-thiadiazoles/oxadiazoles on basic alumina under microwave activation is described. All compounds were screened for their in vitro antibacterial activity against B. lichenformis, 2689, K. aerogens 2281, S. typhimurium 2501, E. herbicola 2491, and P. vulgaris 2027 and found to possess activities comparable to that of the standard drug norfloxacin. Received May 2, 2000. Accepted (revised) June 13, 2000     

Rheological changes occurring during the storage of the system sodium dodecyl sulphate/1-hexadecanol/water

Summary The physical decomposition of the system formed when sodium dodecyl sulphate, 1-hexadecanol and water are heated, mixed and cooled could be achieved at an accelerated rate by cycling the storage temperature between 5–7 °C and 20–25 °C. This decomposition caused the formation of pearliness and the systems became progressively more fluid with loss in rigidity.The changes in the rheological properties of the systems were investigated at 25 °C using a modifiedWeissenberg Rheogoniometer, anEpprecht Rheomat 15 viscometer, and a concentric cylinder air turbine viscometer.The systems are referred to by a code R_x where x is the molar ratio of 1-hexadecanol to sodium dodecyl sulphate. The systems R₁–R₁₀ were examined during temperature cycling for a maximum period of eight days. During this period, the systems R₁–R₄ progressively increased in consistency when examined in continuous shear using anEpprecht Rheomat 15, concentric cylinder viscometer. System R₅ was also examined using anEpprecht Rheomat 15, but after increasing in consistency up to the fourth day, thereafter decreased in consistency. Systems R₃ to R₁₀ were investigated in creep mode. For R₃ and R₄, the compliance progressively decreased over a period of eight days, whereas for systems R₅–R₈ compliance was found to pass through a minimum about four days after preparation and the start of temperature cycling. Thereafter it increased. For R₉ and R₁₀, the creep compliance at one hour increased continuously during the eight day period.

---

Zusammenfassung Beschleunigte Zersetzung des Systems, das beim Erwärmen, Mischen und Kühlen von Natriumdodecylsulfat, 1-Hexadekanol und Wasser entsteht, wurde durch zyklische Temperaturänderungen zwischen 5–7 und 20–25 °C bewirkt. Durch Zersetzung wurde das System perlmutterartig verfärbt und unter Verlust an Festigkeit fließfähiger.Die Änderungen im rheologischen Verhalten wurden mit einem modifiziertenWeissenberg-Rheogoniometer, einem Rheomat-15-Viskosimeter, und einem Luftturbinen-Viskosimeter mit konzentrischen Zylindern untersucht.Auf die verschiedenen Systeme wird mit einem Code R_x Bezug genommen, wobei x das molare Verhältnis von 1-Hexadekanol zu Natriumdodecylsulfat ist. Die Systeme R₁–R₁₀ wurden über einen Zeitraum von 8 Tagen unter dem Einfluß von zyklischen Temperaturänderungen untersucht. Innerhalb dieses Zeitraumes nahmen die flüssigen Systeme R₁–R₄, wie kontinuierliche Scherexperimente mit dem Rheomat 15 Viskosimeter (konzentrische Zylinder) zeigten, beständig an Konsistenz zu. System R₅ wurde auch mit dem Rheomat 15 untersucht; es zeigte aber, nach einer Konsistenzzunahme bis zum 4. Tag, eine Abnahme an Konsistenz. Die Systeme R₆–R₁₀, die mehr Festkörper-Charakter hatten, wurden mit Hilfe von Kriechtesten untersucht. Die dynamische Nachgiebigkeit bei 1 Std. ging durch ein Minimum 4 Tage nach der Herstellung bei Lagerung mit zyklischer Temperaturänderung. Danach nimmt sie zu. Für R₉–R₁₀ nahm die dynamische Nachgiebigkeit bei 1 Std. kontinuierlich über die 8 Tage zu.

---

---

Paper presented to the British Society of Rheology Conference on Rheology in Medicine and Pharmacy, London, April 14–15, 1970.     

Bounds on the CP asymmetry in like-sign dileptons from B(0)B*(0) meson decays

We have measured the charge asymmetry in like-sign dilepton yields from B(0)B*(0) meson decays using the CLEO detector at the Cornell Electron Storage Ring. We find a(0)(ll) identical with[N(l(+)l(+))-N(l(-)l(-))]/[N(l(+)l(+))+N(l(-)l(-))] = +0.013+/-0.050+/-0.005. We combine this result with a previous, independent measurement and obtain Re(epsilon(B))/(1+ the absolute value of epsilon(B)(2)) = +0.0035+/-0.0103+/-0.0015 (uncertainties are statistical and systematic, respectively) for the CP impurity parameter, epsilon(B).