Haemolysis Effect Estimation of Doxycycline Hyclate 150 mgDelay Release Tablet in Bio-analysis (Human Plasma) by LiquidChromatography-Tandem Mass Spectrometry
A fast, simple and particular method for estimation of Doxycycline in healthy human plasma was validated using Minocycline as IS. The analyte and IS were extracted from plasma using SPE. The compound was estranged on a RP column with an isocratic mobile phase consisting of 0.1% formic acid in water and acetonitrile (12:88, v/v), and detected by tandem mass spectrometry in positive ion mode. The ion transition recorded in several reaction monitoring mode were m/z 294.1→225.1 for Doxycycline and m/z 286.1→217.1 for IS. Linearity in plasma was observed over the concentration range 0.3-30 ng/mL for Doxycycline. The mean recovery for Doxycycline was 83.7%, with a lower limit of quantification of 0.3 ng/mL. The coefficient of variation of the assay was less than 6.8%, and accuracy of 96.1% to 102.2%. The validated method was applied to bioequivalence study of 150 mg Doxycycline Hyclate tablet in healthy human volunteers. The validated method was used to expose study samples of bioequivalence study of 150 mg Doxycycline Hyclate delay release tablet in 36 healthy human volunteers. Total 50 samples from individual volunteers identified as Haemolyzed, which were analyze initial and repeat again to cross check the method reproducibity for Haeamolysis effect and compared which found acceptable range. Bioequivalence was prove for test and reference using validated method to experimental samples (Figure 1).
Development and Validation of LC-MS/MS Method for the Simultaneous Determination of Quinine and Doxycycline in Pharmaceutical Formulations
Abstract A fast, sensitive, and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of quinine and doxycycline in pharmaceutical formulations. The LC-MS/MS method was carried out on a Sun Fire Waters C18 column (50 mm × 3.0 mm I.D.) and the mobile phase consisted of acetonitrile:0.1% formic acid (75:25, v/v), run at a flow rate of 0.45 mL/min (split 1:3). The injection volume was 10 µL for both standard and samples. The triple quadrupole mass spectrometer equipped with an electrospray source in positive mode (ES+) was set up in multiple reaction monitoring mode (MRM), monitoring the transitions of 325.0 > 307.0 and 445.0 > 428.1, for quinine and doxycycline, respectively. The total analysis time was 2 min and the method was linear in the concentration range of 10–1500 ng/mL for both compounds. Method validation investigated parameters such as the specificity, linearity, precision, accuracy, and robustness, giving results within the acceptable range. Moreover, the proposed method was successfully applied for determination of quinine and doxycycline in nanocapsule formulations to support the quality control.
Highly enantio- and diastereoselective synthesis of β-methyl-γ-monofluoromethyl-substituted alcohols.
Enanatiopure β-methyl-γ-monofluoromethyl alcohols were prepared from the allylic alkylation between fluorobis(phenylsulfonyl)methane with Morita-Baylis-Hillman carbonates. The reaction was catalyzed by using the Cinchona alkaloid derivative, (DHQD)(2)AQN. The origin of the stereoselectivity was verified by DFT methods. Calculated geometries and relative energies of various transition states strongly support the observed stereoselectivity.