PMID- 30151245
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 2067-0656 (Print)
IS  - 2069-4032 (Electronic)
VI  - 41
IP  - 1
DP  - 2015 Jan-Mar
TI  - Development of a new HPLC method for simultaneous determination of clopidogrel 
      and its major metabolite using a chemometric approach.
PG  - 11-21
LID - 10.12865/CHSJ.41.01.02 [doi]
AB  - This paper presents the development and validation of a new HPLC-UV method for 
      simultaneous quantitative determination of clopidogrel and its hydrolysis product 
      clopidogrel carboxylic acid (CCA) from bulk material and dosage formulations. 
      Development of the chromatographic method is based on a design of experiments 
      (DOE) approach. A Box-Behnken experimental design was used to build the 
      mathematical models and to choose the significant parameters for the optimization 
      by simultaneously taking resolution, capacity factor and peak symmetry as 
      responses. Derringer's desirability function was used for the selection of the 
      optimum experimental conditions in terms of mobile phase composition, column 
      temperature and flow rate. The developed method was validated as per ICH 
      guidelines with respect to specificity, linearity, limit of detection, limit of 
      quantification, accuracy, precision, robustness and system suitability. The 
      method was further employed for the study of clopidogrel bisulfate hydrolysis 
      kinetics under different pH conditions, with special emphasis on the acidic 
      hydrolysis studies, since different clopidogrel salts are suffering pre-systemic 
      metabolism trough hydrolysis under the acidic pH of the stomach. This effect is 
      generally difficult to quantify, since CCA is also the main circulating 
      metabolite, and no differentiation between the pre-systemic and systemic CCA can 
      be made. In the acidic environment created by a 0.1N HCl solution CLO degradation 
      was slow at room or body temperature (25 and 37 degrees C respectively), less than 5% of 
      the initial CLO amount being hydrolyzed after 48h. Under forced conditions (85 masculineC) 
      however, 17.8% of CLO was transformed into CCA within 48 hours.
FAU - Anuta, V
AU  - Anuta V
AD  - "Carol Davila" University of Medicine and Pharmacy, Faculty of Pharmacy, 
      Department of Physical Chemistry, Bucharest, Romania.
FAU - Sarbu, I
AU  - Sarbu I
AD  - "Carol Davila" University of Medicine and Pharmacy, Faculty of Pharmacy, Doctoral 
      School, Bucharest, Romania.
FAU - Mircioiu, I
AU  - Mircioiu I
AD  - Ovidius University, Faculty of Pharmacy, Department of Biopharmacy, Constanta, 
      Romania.
FAU - Velescu, B S
AU  - Velescu BS
AD  - "Carol Davila" University of Medicine and Pharmacy, Faculty of Pharmacy, 
      Department of Pharmacology and Clinical Pharmacy, Bucharest, Romania.
LA  - eng
PT  - Journal Article
DEP - 20150315
PL  - Romania
TA  - Curr Health Sci J
JT  - Current health sciences journal
JID - 101597164
PMC - PMC6057539
OTO - NOTNLM
OT  - Clopidogrel
OT  - Clopidogrel carboxylic acid
OT  - Design of Experiments
OT  - HPLC
OT  - degradation study
EDAT- 2015/01/01 00:00
MHDA- 2015/01/01 00:01
PMCR- 2015/01/01
CRDT- 2018/08/29 06:00
PHST- 2015/02/27 00:00 [received]
PHST- 2015/03/15 00:00 [accepted]
PHST- 2018/08/29 06:00 [entrez]
PHST- 2015/01/01 00:00 [pubmed]
PHST- 2015/01/01 00:01 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 2015.01.02 [pii]
AID - 10.12865/CHSJ.41.01.02 [doi]
PST - ppublish
SO  - Curr Health Sci J. 2015 Jan-Mar;41(1):11-21. doi: 10.12865/CHSJ.41.01.02. Epub 
      2015 Mar 15.