PMID- 16860502
OWN - NLM
STAT- MEDLINE
DCOM- 20061227
LR  - 20181201
IS  - 0378-5173 (Print)
IS  - 0378-5173 (Linking)
VI  - 323
IP  - 1-2
DP  - 2006 Oct 12
TI  - An in vitro investigation on acid catalyzed reactions of proton pump inhibitors 
      in the absence of an electrophile.
PG  - 110-6
AB  - An in vitro investigation of the complex system of acid catalyzed conversions of 
      some proton pump inhibitors (PPI) have been carried out using differential pulse 
      polarographhy (DPP) at the static mercury drop electrode (SMDE). Reactions were 
      investigated in solutions buffered to pH values 2.0-8.0. The employed technique 
      facilitated fast and timely monitoring of each PPI, in addition to its 
      electroactive degradation products. Unlike previous techniques, which employed 
      HPLC and UV spectroscopy, alone, or in combination, DPP facilitated fast and 
      simultaneous recordings of all analytes in situ. This resulted in well-defined 
      current-time profiles of individual electroactive degradation products, in 
      addition to those of the starting materials. The results demonstrated that the 
      rates of degradation of the investigated PPIs can be arranged in the following 
      order: lansoprazole>omeprazole>pantoprazole. Furthermore, the rate of degradation 
      of PPIs decreased with decreasing basicity of the corresponding benzimidazole 
      nitrogen of PPIs, as predicted by the effect of individual substituents on each 
      of the benzimidazole rings. The present study demonstrated that lansoprazole may 
      have the fastest accumulation rate in the parietal cells, in addition to 
      demonstrating the highest rate of conversion into the active inhibitor. At pH 6, 
      however, pantoprazole was found to be the most stable, whereas lansoprazole and 
      omeprazole underwent significant acid catalyzed decomposition. The cyclic 
      sulfenamide of pantoprazole demonstrated highest stability among the three PPIs. 
      Omeprazole, however, fell in the middle in terms of its stability and the 
      stability of its corresponding cyclic sulfenamide. The present study may provide 
      an insight for designing more potent new proton pump inhibitors.
FAU - Tutunji, Maha F
AU  - Tutunji MF
AD  - Chemistry Department, Faculty of Science, University of Jordan, Amman, Jordan. 
      pru@go.com.jo
FAU - Qaisi, Ali M
AU  - Qaisi AM
FAU - El-Eswed, Bassam
AU  - El-Eswed B
FAU - Tutunji, L F
AU  - Tutunji LF
LA  - eng
PT  - Journal Article
DEP - 20060602
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Acids)
RN  - 0 (Anti-Ulcer Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0K5C5T2QPG (Lansoprazole)
RN  - D8TST4O562 (Pantoprazole)
RN  - KG60484QX9 (Omeprazole)
SB  - IM
MH  - 2-Pyridinylmethylsulfinylbenzimidazoles/*chemistry
MH  - Acids/chemistry
MH  - Anti-Ulcer Agents/chemistry
MH  - Catalysis
MH  - Dimerization
MH  - Drug Stability
MH  - Electrochemistry
MH  - Enzyme Inhibitors/chemistry
MH  - Hydrogen-Ion Concentration
MH  - Lansoprazole
MH  - Omeprazole/chemistry
MH  - Pantoprazole
MH  - Polarography
MH  - *Proton Pump Inhibitors
EDAT- 2006/07/25 09:00
MHDA- 2006/12/28 09:00
CRDT- 2006/07/25 09:00
PHST- 2006/03/15 00:00 [received]
PHST- 2006/05/06 00:00 [revised]
PHST- 2006/05/25 00:00 [accepted]
PHST- 2006/07/25 09:00 [pubmed]
PHST- 2006/12/28 09:00 [medline]
PHST- 2006/07/25 09:00 [entrez]
AID - S0378-5173(06)00441-8 [pii]
AID - 10.1016/j.ijpharm.2006.05.057 [doi]
PST - ppublish
SO  - Int J Pharm. 2006 Oct 12;323(1-2):110-6. doi: 10.1016/j.ijpharm.2006.05.057. Epub 
      2006 Jun 2.