Figure 1. picoSpin-45 1H NMR Spectrum of Asprin (1.2 M in DMSO-D6, 64 scans).
Figure 2. picoSpin-45 1H NMR Spectrum of Naproxen (50/50 v/v in CDCl3, 16 scans).
Figure 3. picoSpin-45 1H NMR Spectrum of Chalcone (1.22 M in Acetone-D6 with 1% TMS, 64 scans).
Figure 4. picoSpin-45 1H NMR Spectrum of Benzocaine (1.27 M in CDCl3 with 1% TMS, 64 scans).
Figure 5. picoSpin-45 1H NMR Spectrum of Lidocaine (10 M in CDCl3, 116 scans).
Figure 6. picoSpin-45 1H NMR Spectrum of Procainamide (2.1 M in D2O, 168 scans).
Figure 7. picoSpin-45 1H NMR Spectrum of Procaine (1.5 M in D2O, 168 scans).
Figure 8. picoSpin-45 1H NMR Spectrum of Ibuprofen Soft-Gel (50/50 v/v in CDCl3, 144 scans).
Solution and solid state properties of a set of procaine and procainamide derivatives Original
Research Article
European Journal of Pharmaceutical Sciences, Volume 18, Issue 5, April 2003, Pages 337-348
Marı ́a Eugenia Olivera, Marı ́a Veronica Ramı ́rez Rigo, Ana Karina Chattah, Patricia Rebeca Levstein,
Miria Baschini, Ruben Hilario Manzo View Abstract
Abstract
A set of potential Class III antiarrhythmic agents of structure p-HOOC–R–CO–NH–C6H4–CO–X–C2H5–
N(C2H5)2 were isolated as crystalline solids of the amide and ester derivatives, I:
succinylprocainamide (X=–NH–, R=–C2H4–); II: succinylprocaine (X=–O–, R=–C2H4–); III:
maleylprocainamide (X=–NH–, R=–C2H2–) and IV: maleylprocaine (X=–O–, R=–C2H2–). Although
compounds I–IV exhibit similar solution properties (i.e. acid–base speciation, with zwitterionic (+−)
to neutral (00) form ratios higher than 104), aqueous solubility of –NH– derivatives is significantly
higher than that of –O– derivatives and also, solvent effects on solubility (i.e. the change of water by
ethanol) is clearly different in both series. Solution and solid-state properties of I–IV were
characterized to account for the observed differences. Results indicate that procainamide
derivatives I and III crystallizes as (+−)s but procaine derivatives II and IV as (00)s. Besides, I is
anhydrous but II–IV are hydrates. Aqueous solubility and solvent effect on solubility are controlled
by the intrinsic solubility of the species (+−) in I and III and (00) in II and IV. The rise of hydrophilicity
of species (00) due to the structural change from –O– to –NH– would determine the change in the
structure of the precipitating crystals from (00)s to (+−)s. Solid structure (zwitterionic or neutral), as
well as composition (anhydrous or hydrated) may be recognized as the main factors in determining
the rank of aqueous solubility of the set: (+−)>(+−·H2O)>(00·H2O).
Keywords
Antiarrhythmic;
Solid-state properties; CPMAS 13C-RMN; Solubility equilibrium;
Zwitterionic compounds; Solvent effects; Hydrates; Excess free energy
Simultaneous determination of procaine and para-aminobenzoic acid by LC–MS/MS method
Mugunthu R. Dhananjeyana, Corresponding author contact information, E-mail the corresponding
author,
Crystal Bykowskia,
Jill A. Trendela,
Jeffrey G. Sarvera,
Howard Andob,
Paul W. Erhardta, E-mail the corresponding author
a Center for Drug Design and Development, The University of Toledo, Toledo, OH, USA
b Pfizer Global Research and Development, Ann Arbor Laboratories, MI, USA
Abstract
A sensitive high performance liquid chromatography tandem mass spectrometry (LC–MS/MS)
method has been developed for simultaneous determination of procaine and its metabolite paminobenzoic acid (PABA). N-Acetylprocainamide (NAPA) was used as an internal standard for
procaine and PABA analysis. This assay method has also been validated in terms of linearity, lower
limit of detection, lower limit of quantitation, accuracy and precision as per ICH guidelines.
Chromatography was carried out on an XTerra™ MS C18 column and mass spectrometric analysis
was performed using a Quattro Micro™ mass spectrometer working with electro-spray ionization
(ESI) source in the positive ion mode. Enhanced selectivity was achieved using multiple reaction
monitoring (MRM) functions, m/z 237 → 100, m/z 138 → 120, and m/z 278 → 205 for procaine,
PABA and NAPA, respectively. Retention times for PABA, procaine and NAPA were 4.0, 4.7 and 5.8
min, respectively. Linearity for each calibration curve was observed across a range from 100 nM to
5000 nM for PABA, and from 10 nM to 5000 nM for procaine. The intra- and inter-day relative
standard deviations (RSD) were <5%.
Keywords
Esters; LC–MS/MS; Local anesthetics; NAPA; PABA Procaine