Journal of Pharmaceutical Analysis - 华体会 iOS下载

Development of forced degradation and stability indicating studies of drugs-A review

Blessy Mn, Ruchi D. Patel, Prajesh N. Prajapati, Y.K. Agrawal

Blessy Mn, Ruchi D. Patel, Prajesh N. Prajapati, Y.K. Agrawal Forced degradation is a degradation of new drug substance and drug product at conditions more severe than accelerated conditions. It is required to demonstrate specificity of stability indicating methods and also provides an insight into degradation pathways and degradation products of the drug substance and helps in elucidation of the structure of the degradation products. Forced degradation studies show the chemical behavior of the molecule which in turn helps in the development of formulation and package. In addition, the regulatory guidance is very general and does not explain about the performance of forced degradation studies. Thus, this review discusses the current trends in performance of forced degradation studies by providing a strategy for conducting studies on degradation mechanisms and also describes the analytical methods helpful for development of stability indicating method. Journal of Pharmaceutical Analysis. 2014 ${article.volume}(3): 159-165.

Direct detection and identification of active pharmaceutical ingredients in intact tablets by helium plasma ionization (HePI) mass spectrometry

Athula B. Attygalle, Freneil B. Jariwala, Julius Pavlov, Zhihua Yang, Jason A. Mahr, Mabel Oviedo A simple modification converts an electrospray ion source to an ambient-pressure helium plasma ionization source without the need of additional expensive hardware. Peaks for active ingredients were observed in the spectra recorded from intact pharmaceutical tablets placed in this source. A flow of heated nitrogen was used to thermally desorb analytes to gas phase. The desorption temperatures were sometimes as low as 50 1C. For example, negative-ion spectra recorded from an aspirin tablet showed peaks at m/z 137 (salicylate anion) and 179 (acetylsalicylate anion) which were absent in the background spectra. The overall ion intensity increased as the desorption gas temperature was elevated. Within the same acquisition experiment, both positive- and negative-ion signals for acetaminophen were recorded from volatiles emanating from Tylenol tablets by switching the polarity of the capillary back and forth. Moreover, different preparations of acetaminophen tablets could be distinguished by their ion-intensity thermograms. Journal of Pharmaceutical Analysis. 2014 ${article.volume}(3): 166-172.

Derringer desirability and kinetic plot LC-column comparison approach for MS-compatible lipopeptide analysis

Matthias D’Hondt, Frederick Verbeke, Sofie Stalmans, Bert Gevaert, Evelien Wynendaele, Bart De Spiegeleern Lipopeptides are currently re-emerging as an interesting subgroup in the peptide research field, having historical applications as antibacterial and antifungal agents and new potential applications as antiviral, antitumor, immune-modulating and cell-penetrating compounds. However, due to their specific structure, chromatographic analysis often requires special buffer systems or the use of trifluoroacetic acid, limiting mass spectrometry detection. Therefore, we used a traditional aqueous/acetonitrile based gradient system, containing 0.1% (m/v) formic acid, to separate four pharmaceutically relevant lipopeptides (polymyxin B1, caspofungin, daptomycin and gramicidin A1), which were selected based upon hierarchical cluster analysis (HCA) and principal component analysis (PCA).
In total, the performance of four different C18 columns, including one UPLC column, were evaluated using two parallel approaches. First, a Derringer desirability function was used, whereby six single and multiple chromatographic response values were rescaled into one overall D-value per column. Using this approach, the YMC Pack Pro C18 column was ranked as the best column for general MS-compatible lipopeptide separation. Secondly, the kinetic plot approach was used to compare the different columns at different flow rate ranges. As the optimal kinetic column performance is obtained at its maximal pressure, the length elongation factorλ(Pmax/Pexp) was used to transform the obtained experimental data (retention times and peak capacities) and construct kinetic performance limit (KPL) curves, allowing a direct visual and unbiased comparison of the selected columns, whereby the YMC Triart C18 UPLC and ACE C18 columns performed as best. Finally, differences in column performance and the (dis)advantages of both approaches are discussed. Journal of Pharmaceutical Analysis. 2014 ${article.volume}(3): 173-183.

Combined collision-induced dissociation and photo-selected reaction monitoring mass spectrometry modes for simultaneous analysis of coagulation factors and estrogens

Quentin Enjalbert, Marion Girod, Jérémy Jeudy, Jordane Biarc, Romain Simon, Rodolphe Antoine, Philippe Dugourd, Jér?me Lemoine, Arnaud Salvador Oral estrogens are directly associated with changes in plasma levels of coagulation proteins. Thus, the detection of any variation in protein concentrations due to estrogen contraceptives, by a simultaneous analysis of both coagulation proteins and estrogens, would be a very informative tool. In the present study, the merit of photo-selected reaction monitoring (SRM), a new analytical tool, was evaluated towards estrogens detection in plasma. Then, SRM and photo-SRM detection modes were combined for the simultaneous analysis of estrogen molecules together with heparin co-factor and factor XIIa, two proteins involved in the coagulation cascade. This study shows that photo-SRM could open new multiplexed analytical routes. Journal of Pharmaceutical Analysis. 2014 ${article.volume}(3): 183-189.

Profiling the dynamics of abscisic acid and ABA-glucose ester after using the glucosyltransferase UGT71C5 to mediate abscisic acid homeostasis in Arabidopsis thaliana by HPLC-ESI-MS/MS

Dong-Mei Xiong, Zhen Liu, Han Chen, Jin-Tao Xue, Yi Yang, Cong Chen, Li-Ming Ye

Dong-Mei Xiong, Zhen Liu, Han Chen, Jin-Tao Xue, Yi Yang, Cong Chen, Li-Ming Ye The HPLC-MS/MS method was developed to profile the dynamics of abscisic acid (ABA) and ABA-glucose ester (ABA-GE) after cloning glycosyltransferase enzyme family gene AtUGT71C5 into Arabidopsis thaliana. By constructing over-expression lines (OE) and down-expression lines (DN), we acquired mutant strains to analyze the function of AtUGT71C5. The multiple-reaction monitoring (MRM) was used for quantitative determination in negative mode. The transition was m/z 263.1-153.0 for ABA ([M-H]t), m/z 425.1-263.0 for ABA-GE ([M-H]t), and m/z 321.0-152.0 for chloramphe-nicol. The linear range was 0.8684-217.1 ng/mL for ABA and 0.3920-196.0 ng/mL for ABA-GE. The accuracy was 88.0-109.0% for ABA and 86.6-113.0% for ABA-GE; the inter-day and intra-day precisions were less than 5.4%for ABA and 8.9%for ABA-GE, respectively. This method is simple and sensitive enough for determination of ABA and ABA-GE in A. thaliana leaves. All the evidence confirmed the speculation that AtUGT71C5 can mediate abscisic acid homeostasis. Journal of Pharmaceutical Analysis. 2014 ${article.volume}(3): 190-196.

Enantiomeric characterization and structure elucidation of Otamixaban

Jian Shen, Jiping Yang, Winfried Heyse, Harald Schweitzer, Norbert Nagel, Doris Andert, Chengyue Zhu, Vincent Morrison, Gregory A. Nemeth, Teng-Man Chen, Zhicheng Zhao, Timothy A. Ayers, Yong-Mi Choi Otamixaban is a potent (Ki ? 0.5 nM) fXa inhibitor currently in late-stage clinical develop-ment at Sanofi for the management of acute coronary syndrome. Being unproductive in obtaining a suitable crystal of Otamixaban, the required enantiomeric characterization has been accomplished using vibrational circular dichroism (VCD) spectroscopy. Selected by a spectrum similarity index, the calculated spectra of several higher energy conformers were found to match well with the observed spectra. The characteristic IR bands of these conformers were also identified and attributed to the solvation effect. Combined with both the single crystal x-ray diffraction results for an intermediate and the proton NMR study, the absolute configuration of Otamixaban is unambiguously determined to be (R,R). Journal of Pharmaceutical Analysis. 2014 ${article.volume}(3): 197-204.

Determination of mycophenolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry

Vivek Upadhyay, Vikas Trivedi, Gaurang Shah, Manish Yadav, Pranav S. Shrivastav

Vivek Upadhyay, Vikas Trivedi, Gaurang Shah, Manish Yadav, Pranav S. Shrivastav A simple, sensitive and high throughput ultra performance liquid chromatography tandem mass spectrometry method has been developed for the determination of mycophenolic acid in human plasma. The method involved simple protein precipitation of MPA along with its deuterated analog as an internal standard (IS) from 50 mL of human plasma. The chromatographic analysis was done on Acquity UPLC C18 (100mm*2.1mm,1.7mm) column under isocratic conditions using acetonitrile and 10 mM ammonium formate, pH 3.00 (75:25, v/v) as the mobile phase. A triple quadrupole mass spectrometer operating in the positive ionization mode was used for quantitation. In-source conversion of mycophenolic glucuronide metabolite to the parent drug was selectively controlled by suitable optimization of cone voltage, cone gas flow and desolvation temperature. The method was validated over a wide concentration range of 15–15000 ng/mL. The mean extraction recovery for the analyte and IS was 495%. Matrix effect expressed as matrix factors ranged from 0.97 to 1.02. The method was successfully applied to support a bioequivalence study of 500 mg mycophenolate mofetil tablet in 72 healthy subjects. Journal of Pharmaceutical Analysis. 2014 ${article.volume}(3): 205-216.

Quality analysis of commercial samples of Ziziphi spinosae semen (suanzaoren) by means of chromatographic fingerprinting assisted by principal component analysis

Shuai Sun, Hailing Liu, Shunjun Xu, Yuzhen Yan, Peishan Xie

Shuai Sun, Hailing Liu, Shunjun Xu, Yuzhen Yan, Peishan Xie Due to the scarcity of resources of Ziziphi spinosae semen (ZSS), many inferior goods and even adulterants are generally found in medicine markets. To strengthen the quality control, HPLC fingerprint common pattern established in this paper showed three main bioactive compounds in one chromatogram simultaneously. Principal component analysis based on DAD signals could discriminate adulterants and inferiorities. Principal component analysis indicated that all samples could be mainly regrouped into two main clusters according to the first principal component (PC1, redefined as Vicenin II) and the second principal component (PC2, redefined as zizyphusine). PC1 and PC2 could explain 91.42%of the variance. Content of zizyphusine fluctuated more greatly than that of spinosin, and this result was also confirmed by the HPTLC result. Samples with low content of jujubosides and two common adulterants could not be used equivalently with authenticated ones in clinic, while one reference standard extract could substitute the crude drug in pharmaceutical production. Giving special consideration to the well-known bioactive saponins but with low response by end absorption, a fast and cheap HPTLC method for quality control of ZSS was developed and the result obtained was commensurate well with that of HPLC analysis. Samples having similar fingerprints to HPTLC common pattern targeting at saponins could be regarded as authenticated ones. This work provided a faster and cheaper way for quality control of ZSS and laid foundation for establishing a more effective quality control method for ZSS. Journal of Pharmaceutical Analysis. 2014 ${article.volume}(3): 217-222.

Application of analytical instruments in pharmaceutical analysis

Journal of Pharmaceutical Analysis. 2014 ${article.volume}(3): 223-226.