Girish Deshpande - Academia.edu (original) (raw)
Papers by Girish Deshpande
Organic Process Research & Development, 2014
ABSTRACT During process development, it is always a debatable issue whether the variation in anal... more ABSTRACT During process development, it is always a debatable issue whether the variation in analytical results is due to the measurement system or due to process. Best approach is to quantify total variation coming from the measurement system prior to any process improvement activity. This quantification is done by Gage R & R. This article describes the use of Gage R & R concept for quantifying the variation from the various sources and for selecting a suitable measurement system for the analysis.. In present article, potentiometer and UPLC equipment were evaluated for the assay measurement of a KSM supplied by a vendor. After GRR study, it was found that the potentiometer was not the suitable instrument because of the high variation contributed by it, whereas UPLC was found to be suitable because of the insignificant variation contributed by it toward the assay. Further it was observed that the variation contributed by the KSM samples was insignificant indicating that those samples were coming from a robust process and vendor was found to be suitable for supplying the KSM.
Journal of Pharmaceutical and Biomedical Analysis, 2011
In the impurity profile of naproxen around 0.6% unknown polar impurity was detected by high perfo... more In the impurity profile of naproxen around 0.6% unknown polar impurity was detected by high performance liquid chromatography (HPLC). The product ion spectrum of the impurity and Naproxen was recorded in LCMS/MS and the fragmentation pattern of the impurity was observed to be similar to the fragmentation pattern of Naproxen with only a difference of two atomic mass units. The high resolution mass spectrum (HRMS) of the impurity displayed a protonated molecular ion at m/z 229.0863, which corresponds to the pseudomolecular formula C 14 H 13 O 3 + . Based on LC/MS/MS, HRMS, 1D and 2D NMR data, the structure of the impurity was characterized as 2-(6-methoxynaphthalen-2-yl)acrylic acid. The acrylic acid impurity was synthesized in the laboratory and co injected in HPLC to confirm the retention time. RRF of the impurity was determined by 1 H NMR method and also by conventional HPLC slope method and the RRF values are found to be 6.11 and 5.64, respectively. The values are comparable and 1 H NMR method of RRF determination is complimentary and can be effectively used as an alternative method to conventional HPLC method especially in early stages of development when availability of impurity standards is not possible.
Chromatographia, 2008
A simple reverse phase liquid chromatographic method was developed for the quantitative determina... more A simple reverse phase liquid chromatographic method was developed for the quantitative determination of desipramine hydrochloride and its related impurities in bulk drugs which is also stability-indicating. During the forced degradation at hydrolysis, oxidative, photolytic and thermal stressed conditions, the degradation results were only observed in the oxidative stress condition. The blend of the degradation product and potential impurities were used to optimize the method by an YMC Pack Pro C 18 stationary phase. The LC method employs a linear gradient elution with the water-acetonitrile-trifluoroacetic acid as mobile phase. The flow rate was 1.0 mL min -1 and the detection wavelength 215 nm. The stressed samples were quantified against a qualified reference standard and the mass balance was found close to 99.0% (w/w) when the response of the degradant was considered to be equal to the analyte (i.e. desipramine). The developed RP-LC method was validated in agreement with ICH requirements.
Chromatographia, 2011
As over 70% of pharmaceutical compounds are bases, the analysis of these basic compounds by high ... more As over 70% of pharmaceutical compounds are bases, the analysis of these basic compounds by high performance liquid chromatography (HPLC) continues to be of great value and interesting. Acetyl cholinesterase inhibitors (AChEIs), which contain the basic compounds like Rivastigmine tartrate, Galantamine hydrobromide and Donepezil with different polarities, were chosen for the study. A rapid screening of the volatile ion-pairing reagents
Organic Process Research & Development, 2013
ABSTRACT It has been observed that the main focus during the process development and manufacturin... more ABSTRACT It has been observed that the main focus during the process development and manufacturing of an API is to meet the customer’s specifications (LSL and USL) rather than estimating and improving the natural control limits (LCL and UCL) of the process. It results in the overlap of the natural control limit and customer’s specification, which in turn increases the chance of failure with respect to the customer’s specifications. A better approach is to work on decreasing the variability of the process so that natural control limits become much tighter than customer’s specification. The statistical control charts not only help in estimating these internal/natural control limits but also raises an alert when the process goes out of control. These alerts trigger the investigation through root cause analysis leading to the process improvements which in turn lead to the decrease in variability of the process. This process continues till inherent variability of the process is due to common causes only and cannot be attributed to assignable causes. At this point, the natural control limits of the process can be taken as internal specification for an output quality parameter.
Organic Process Research & Development, 2014
ABSTRACT During process development, it is always a debatable issue whether the variation in anal... more ABSTRACT During process development, it is always a debatable issue whether the variation in analytical results is due to the measurement system or due to process. Best approach is to quantify total variation coming from the measurement system prior to any process improvement activity. This quantification is done by Gage R & R. This article describes the use of Gage R & R concept for quantifying the variation from the various sources and for selecting a suitable measurement system for the analysis.. In present article, potentiometer and UPLC equipment were evaluated for the assay measurement of a KSM supplied by a vendor. After GRR study, it was found that the potentiometer was not the suitable instrument because of the high variation contributed by it, whereas UPLC was found to be suitable because of the insignificant variation contributed by it toward the assay. Further it was observed that the variation contributed by the KSM samples was insignificant indicating that those samples were coming from a robust process and vendor was found to be suitable for supplying the KSM.
Journal of Pharmaceutical and Biomedical Analysis, 2011
In the impurity profile of naproxen around 0.6% unknown polar impurity was detected by high perfo... more In the impurity profile of naproxen around 0.6% unknown polar impurity was detected by high performance liquid chromatography (HPLC). The product ion spectrum of the impurity and Naproxen was recorded in LCMS/MS and the fragmentation pattern of the impurity was observed to be similar to the fragmentation pattern of Naproxen with only a difference of two atomic mass units. The high resolution mass spectrum (HRMS) of the impurity displayed a protonated molecular ion at m/z 229.0863, which corresponds to the pseudomolecular formula C 14 H 13 O 3 + . Based on LC/MS/MS, HRMS, 1D and 2D NMR data, the structure of the impurity was characterized as 2-(6-methoxynaphthalen-2-yl)acrylic acid. The acrylic acid impurity was synthesized in the laboratory and co injected in HPLC to confirm the retention time. RRF of the impurity was determined by 1 H NMR method and also by conventional HPLC slope method and the RRF values are found to be 6.11 and 5.64, respectively. The values are comparable and 1 H NMR method of RRF determination is complimentary and can be effectively used as an alternative method to conventional HPLC method especially in early stages of development when availability of impurity standards is not possible.
Chromatographia, 2008
A simple reverse phase liquid chromatographic method was developed for the quantitative determina... more A simple reverse phase liquid chromatographic method was developed for the quantitative determination of desipramine hydrochloride and its related impurities in bulk drugs which is also stability-indicating. During the forced degradation at hydrolysis, oxidative, photolytic and thermal stressed conditions, the degradation results were only observed in the oxidative stress condition. The blend of the degradation product and potential impurities were used to optimize the method by an YMC Pack Pro C 18 stationary phase. The LC method employs a linear gradient elution with the water-acetonitrile-trifluoroacetic acid as mobile phase. The flow rate was 1.0 mL min -1 and the detection wavelength 215 nm. The stressed samples were quantified against a qualified reference standard and the mass balance was found close to 99.0% (w/w) when the response of the degradant was considered to be equal to the analyte (i.e. desipramine). The developed RP-LC method was validated in agreement with ICH requirements.
Chromatographia, 2011
As over 70% of pharmaceutical compounds are bases, the analysis of these basic compounds by high ... more As over 70% of pharmaceutical compounds are bases, the analysis of these basic compounds by high performance liquid chromatography (HPLC) continues to be of great value and interesting. Acetyl cholinesterase inhibitors (AChEIs), which contain the basic compounds like Rivastigmine tartrate, Galantamine hydrobromide and Donepezil with different polarities, were chosen for the study. A rapid screening of the volatile ion-pairing reagents
Organic Process Research & Development, 2013
ABSTRACT It has been observed that the main focus during the process development and manufacturin... more ABSTRACT It has been observed that the main focus during the process development and manufacturing of an API is to meet the customer’s specifications (LSL and USL) rather than estimating and improving the natural control limits (LCL and UCL) of the process. It results in the overlap of the natural control limit and customer’s specification, which in turn increases the chance of failure with respect to the customer’s specifications. A better approach is to work on decreasing the variability of the process so that natural control limits become much tighter than customer’s specification. The statistical control charts not only help in estimating these internal/natural control limits but also raises an alert when the process goes out of control. These alerts trigger the investigation through root cause analysis leading to the process improvements which in turn lead to the decrease in variability of the process. This process continues till inherent variability of the process is due to common causes only and cannot be attributed to assignable causes. At this point, the natural control limits of the process can be taken as internal specification for an output quality parameter.