emerging instrumental analytical techniques used in

Zagade et al. World Journal of Pharmaceutical Research

www.wjpr.net Vol 9, Issue 8, 2020.

774

EMERGING INSTRUMENTAL ANALYTICAL TECHNIQUES USED

IN PHARMACEUTICAL ANALYSIS: A REVIEW

Pratik R. Zagade*1, Nikhil N. Kumbhar

2, Kirti S. Raut

1 and Rutuja U. Thombare

1

1Department of Pharmaceutical Chemistry, Seth Govind Raghunath Sable College of

Pharmacy, Saswad, Pune.

2Department of Pharmaceutics, Seth Govind Raghunath Sable College of Pharmacy, Saswad,

Pune.

ABSTRACT

These pharmaceuticals would assist their intent best if they may be free

from impurities and are administered in the proper quantity. Hence,

there are having many demanding situations and it may be decreased

by productive use of excipients, which permits formulators to triumph

over these demanding situations. So, various chemical and

instrumental techniques had been evolved to make drugs serve their

purpose at normal intervals which are involved inside the estimation of

drugs. These prescribed drugs may broaden impurities at numerous

steps in their development, transportation and storage, which makes

the pharmaceutical sensitive to be administered hence they need to be

recognized and quantitated. For this analytical instrumentation and

strategies play a crucial role. This review highlights the function of

emerging analytical instrumentation and analytical techniques, which includes titrimetric,

chromatographic, spectroscopic, electrophoretic, and electrochemical and their corresponding

strategies which have been applied inside the analysis of pharmaceuticals for determine the

quality of the drugs.

KEYWORDS: Pharmaceuticals, Analytical Techniques, chromatography, spectroscopy,

analysis.

1. INTRODUCTION

In the present stage, the number of drugs and combination of their drug formulations are

introduced progressively into the market at a high rate. Formulation can be designed

World Journal of Pharmaceutical Research SJIF Impact Factor 8.084

Volume 9, Issue 8, 774-796. Review Article ISSN 2277– 7105

Article Received on

01 June 2020,

Revised on 22 June 2020,

Accepted on 13 July 2020,

DOI: 10.20959/wjpr20208-18173

*Corresponding Author

Pratik R. Zagade

Department of

Pharmaceutical Chemistry,

Seth Govind Raghunath

Sable College of Pharmacy,

Saswad, Pune.



775

according to the route of administration.[1]

In these several drugs or formulations may be

either new entities or partial structural modifications of currently ones or novel dosage forms

and multicomponent dosage forms. As here, increasing interest of multicomponent

formulation due to their multiple actions such as greater patient acceptability, quicker relief,

increase potency and fewer side effects. However, in the development and formulation of

dosage forms there are many challenges and it can be minimized by efficacious utilization of

excipients, which sanctions formulators to surmount these challenges. Moreover, Regulatory

guidance provides only constrained details of the requisites for the data sets associated with

the pharmaceutical development[2]

but more detailed information is available for the

toxicological assessment of excipients.[3]

Reactions can occur in the dosage form when the

drug substance is reactive and may be expedited by physical and chemical interaction with

excipients. In some cases, excipients do not interact chemically but stimulate the degradation

of drug substance.

As we know that analytical chemistry is play paramount role in the fields of science and

medicine and it is linked with the disseverment, identification and quantification of the

chemical components. Mostly, it deals with the two aspects of chemical characterization i.e.

qualitative (what it is) and quantitative (how much it is). In addition to qualitative analysis is

diagnosed by way of colour, odour or melting point, beside Quantitative analysis is achieved

by means of quantification of weight or volume. However, different analytical methods are

routinely being utilized for analyzing the drug samples in bulk, pharmaceutical formulation

and organic or biological fluids.

Analytical techniques may be separated into non instrumental and instrumental. Here, in non-

instrumental techniques (wet chemistry methods) are used for separations along with

precipitation, extraction, and distillation. Now, in instrumental methods are constructed for

measuring to some physical properties of substance is evaluated its chemical composition

through the usage of instrument. Newly, the assay strategies within the monographs

encompass chromatography, titrimetry, spectrometry and capillary electrophoresis; also, the

electro analytical strategies can be seen inside the literature.

Therefore, Drug analysis shows the important role in the development of drugs,

manufacturing along with their therapeutic use. Pharmaceutical industries depend upon

quantitative chemical analysis, to make sure the high-quality, purity and efficacy of the raw

material used and final product obtained meet the desired specifications. Thus, for newly



776

delivered pharmaceutical formulations, it becomes vital to increase new analytical techniques

because from time to time the dosage form includes other substances which probably

interfere inside the assay and if not corrected can also impart a systemic error to the assay.

And also, for drug or drug combination might not be authentic in any pharmacopoeias and

thus, no analytical approach for quantification is available. Therefore, different analytical

methods are used to check the excellent requirements of the dosage shape. In addition to

Modern analytical strategies are also playing key function in assessing chemical quality

standards of medicine. Thus, analytical techniques are required for fixing their standards of

medicines and its everyday checking. Thus, the overview highlights a variety of emerging

analytical, chromatographic and instrumental approach developed consisting of

spectrophotometer; HPLC, HPTLC, and GC have wide software in assuring the best and

quantity of pharmaceutical products and those instrumental strategies are simple, precise,

speedy and reproducible as compared to non- instrumental strategies.[4]

2. ANALYTICAL TECHNIQUES

2.1. Titrimetric techniques

In 18th

century, it was year 1835 when French chemist and physicist Joseph Louis Gay-

Lussac invented titrimetric method of analysis, the volumetric technique which results in the

originates the term as titration. Now, there some innovation techniques have been used, i.e.,

spreading of non-aqueous titration method, expanding the applied field of titrimetric methods

to weak acids, bases and potentiometric end points detection enhancing the precision of the

methods. Through the improvement of functional group analysis approaches titrimetric

techniques had been proven to be useful in kinetic measurements which can be in applied to

set up reaction rates. It has a few benefits which include saving time and labor, also greater

precise approach, the reason that is no need of the use of reference standards. For instances,

in the beyond albendozole, captopril and gabapentin in commercial dosage forms become

decided with the aid of titrimetric techniques.[5-7]

The determination of Sparfloxacin the non-

aqueous titration method has been used.[8]

Moreover, to its application in drug determination

titrimetry has been used in the past for the evaluation of degradation products of the

pharmaceuticals.[9]

2.2 Chromatographic techniques

In 1903, Russian-Italian botanist Tswett who invented chromatography technique. During

1970’s, different strategies which includes thin-layer chromatography, open-column

https://en.wikipedia.org/wiki/Botanist

https://en.wikipedia.org/wiki/Chromatography



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chromatography and paper chromatography are involved in maximum chemical separations.

Primarily, chromatography is a separation method that separates mixtures in to individual

components by way of the usage of mobile and stationary phase. The constituents of relative

mixture move at different speed for causing them to separate.

The separation of compounds is relying on differential partitioning between the mobile and

stationary phase. When the stationary phase is a solid support of adsorptive nature and mobile

phase is liquid or gaseous phase it is referred to as adsorption Chromatography. Analytical

chromatography is done usually with lesser quantities of material or mixtures and is for

measuring the relative proportions of analytes in a mixture. According to USP

chromatography may be described as a technique by using which solute are separated by

means of a differential migration method in a gadget consisting of two or more phases, one in

every of which move constantly in a given direction.

2.2.1. Thin layer chromatography

As Thin layer chromatography (TLC) is an old technique still it finds a lot of application in

the field of pharmaceutical analysis. In this technique, a solid phase, the adsorbent, is coated

onto a solid support as a thin layer usually on a glass, plastic, or aluminium support.

Several factors determine the efficiency of this kind of chromatographic separation. First the

adsorbent should show extreme selectivity in the direction of the substance being separated in

order to the dissimilarities inside the fee of elution be large. For the separation of any given

mixture depends upon absorptive power these are too strong to adsorb or too weak to adsorb.

Here, lists of some adsorbents within the order of adsorptive power.[11]

Table 1: Chromatographic absorbents.[10]

Sr.no. Most strong adsorbent Least strong adsorbent

1. Alumina (Al2O3) Silica gel (SiO2)

2. Charcoal (C)

3. Florisil (MgO/SiO2) anhydrous

Thin layer chromatography (TLC) is a suitable technique for the analysis of a large variety of

organic and inorganic materials, due to its distinctive benefits such as minimum sample

clean-up, flexibility in sample characteristic, wide preference of mobile phases, high sample

loading capacity and low cost.[11]



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For analyzing unknown materials in bulk drugs TLC is an effective tool.[12]

It provides a

relatively high degree of declaration that all probable components of the drug are separated.

TLC at the high precision used to quantitative analytical purpose using spot elution and then

followed by spectrophotometric measurement. Determination of some steroid’s TLC has

been applied pioglitazone[13,14]

celecoxib.[15]

TLC performs a vital role inside the early stage

of drug development when records about the impurities and degradation products in drug

product and drug substance is inadequate. Various impurities of pharmaceuticals have been

screened and evaluated by using TLC.[16]

The determination of herbal products i.e.,

Snowdrops (Galanthus L.) is determined by TLC and UV spectrophotometry.[17]

2.2.3. High-performance liquid chromatography (HPLC)

HPLC is one of the advanced technique of liquid chromatography, invented first time in the

year 1980, for bulk drug materials during assay condition.[18]

Here, HPLC technique used for

separating the complex mixture of molecules or substances encountered in biological and

chemical systems, in order to admit better the role of individual molecules.

The specificity of the HPLC technique is superior and simultaneously sufficiently precise and

accurate. At the time of literature survey, it was realized that HPLC has been the maximum

broadly used technique over all of the chromatographic techniques. Table 2 indicates the

assessment of high-performance liquid chromatography of different dosage forms with

mobile phase, which might be taken by a number of the reviewed publications.

In liquid chromatography the selection of detection approach is crucial to guarantee that all

the components are detected. One of the broadly used detectors in HPLC is UV detector

which is able to monitoring several wavelengths concurrently; this is possible because of

applying a multiple wavelength scanning program. As in enough quantity, UV detector

assures all the UV-absorbing components are detected.

PDA i.e., a photodiode array is a coated array of discrete photodiodes on an integrated circuit

(IC) chip for spectroscopy. It is placed at the photograph plane of a spectrometer to permit a

range of wavelengths to be sensed concurrently. When a variable wavelength detector

(VWD) is used with changing wavelength, a sample must be injected numerous times, to

make sure that all of the peaks are detected. In the case of PDA, when it used a wavelength

range can be programed and all the compounds that absorb within this range may be

recognized in a single analysis. PDA detector also can examine pick purity by matching



779

spectra inside a peak. PDA detector finds its application in the technique improvement of

Iloperidone in pharmaceuticals.[19]

The refractive index detector is the detector of choice whilst one desires to detect analytes

with restrained or no UV absorption which include sugars, alcohols, carbohydrates, fatty

acids, and polymers. This detector is having the shortest sensitivity amongst all detectors but

suitable at excessive analyte concentrations.

In the pharmaceutical formulation, to evaluate the content material of volgibose Lakshmi and

Rajesh used the refractive index detector.[20]

The electrochemical detector answered to the

substances that are both oxidizable or reducible and the electric output results from an

electron flow induced with the aid of the chemical reaction that takes place at the surface of

the electrode. This detector was carried out recently to investigate the content of glutathione

in human prostate most cancers cells and lung adenocarcinoma cells.[21]

One of the maximum sensitive detectors some of the LC detectors is fluorescence detector.

Commonly, the sensitivity of this detector is 10–1000 times higher as compare to the UV

detector for active UV absorbing materials used as an advantage that measurement of unique

fluorescent species in samples. One of the maximum vital applications of fluorescence is the

estimation of pharmaceuticals.[22]

Over certain period of time, most analyst used the reversed-phase technique with the help of

UV absorbance detection, because this implement the surpasses available analysis time,

reliability, repeatability and sensitivity. Various drugs have been assayed in pharmaceutical

formulations[23,24]

and in biological fluids[25,26]

by use of HPLC. Thus, HPLC provides a

primary service in answering many questions posed by the pharmaceutical industry.

However, the risks of HPLC consist of solvents, free of columns and a lack of long-time

period reproducibility because of the nature of column packing. Liquid chromatography

linked with mass spectrometry (LC–MS) is taken to consideration as one of the maximum

crucial techniques of the last decade of 20th century. Within pharmaceutical industry the

analytical field in many stages of quality control and assurance is depends on the HPLC

method.[27,28]

Currently, HPLC-MS has been used for determination of purity of drugs.[29-33]

In

addition to its utility in analyzing the drugs HPLC alone and with hyphenated technique have

been used to analyze the impurities of the pharmaceuticals[34,35]

and degradation

products.[36,37]

Development of HPLC methods for simultaneous analysis of antiretrovirals in



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pharmaceutical formulations.[38]

Using Rp-Hplc method In vitro metabolic stability study of

new cyclen based antimalarial drugs.[39]

Table 2: Different dosage forms with mobile phase used during high performance liquid

chromatography.[40-47]

Sr. No. Name of drug Mobile phase

1.

Guaiphenesin phenylephedrine HCl,

Paracetamol, chlorpheniramine maleate and

bromhexine HCl

Methanol and acetonitrile (3:2)

2. Clarithromycin powder Acetonitrile 0.035 mol l-1 pott. Di-

hydrogen ortho-phosphate

3. Phenylepherine, paracetamol, caffeine and

chlorpheniramine

Acetonitrile, MeoH, 10mm

phosphate buffer 16:22:62v/v

4. Ibuprofen and diphenhydramine Hcl -

5. Codeine phosphate, ephedrine HCl and

chlorpheniramine maleate

Methanol, glacial acetic acid,

triethylamine (980:15:6 v/v)

6. Pseudoephedrine HCl, fexofenadine HCl

cetirizine .2 HCl

Tea solution; MeoH; acetonitrile

(50:20:30, v/v/v).

7.

Phenylpropanolamine HCl, Caffeine,

paracetamol, glycerylguaiacolate;

chlorpheniramine maleate

Consisting of a mixture of acnion

pair solution (15:85, v/v)

8. Telmisartan, amlodipine besylate and

hydrochloro-thiazide

Orthophosphoric acid: ACN

(60:40) CHCl3: MeoH formic acid

85:15:5

2.2.3 High performance thin layer chromatography (HPTLC)

Further advancement of the technique, high performance thin layer chromatography

(HPTLC) arrive as an important technique in analysis of drug. HPTLC is a rapid separation

technique and flexible sufficient to investigate a various range of samples. One of the

advantages of this technique is it is simple to handle and requires a short analysis time to

analyze the complex mixtures or the crude sample cleanup. Also, this can be evaluates the

entire chromatogram with a variety of parameters without time limits. Furthermore, there is

simultaneous but independent development of more than one samples and standards on each

plate, leading to an accelerated reliability of results. This technique has been used to

quantitate drugs such as alfuzosin,[48]

ethinyl estradiol and cyproterone,[49]

Aceclofenac,

paracetamol and tramadol.[50]

Literature survey emphasizes that the importance of this

technique along with their challenges and opportunities of the HPTLC.[51,52]

Densitometric

analysis is also done by HPTLC method for Amlodipine, Hydrochlorothiazide, Lisinopril and

Valsartan.[53]

HPTLC Fingerprinting for Quality Control of an Herbal Drug - The Case of

Angelica gigas Root can be done.[54]



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Table 3 shows different steps applicable to this technique during method development,

validation and quantitative analysis i.e., estimation of some category of drugs are as follows-

Table 3: Estimation of some category of drugs by using HPTLC technique.[55-66]

Sr.no. Category of drugs Drugs

1. Analgesics/anti-inflammatory

Paracetamol/piroxicam

Ibuprofen

Dexibuprofen

2. Cardiovascular agent

NevibololHCl

Ranolazine

Telmisartan/ramipril

3. Antibiotics/anti infective Azithromycin

Cefetamet

4. Antiretroviral Emtricitabine/tenofovir

Lamivudine/stavudine/ Nevirapine

5. Antipsychotic/anticonvulsant/Anxiolytic Duloxetine HCl

Risperidone

2.2.4. Gas chromatography (GC)

Moving in advance with any other chromatographic technique, gas chromatography is an

effective separation approach for detection of volatile organic compounds. Combining

separation and online detection permits accurate quantitative evaluation of complex mixtures,

together with traces of compounds down to parts per trillions in some particular cases. Gas

liquid chromatography carries a huge role in the analysis of pharmaceutical product.[67]

The

production of high-molecular mass products inclusive of polypeptides, or thermally volatile

antibiotics bounds the scope of this approach.

Currently, assay of drugs carried out with help of gas chromatography such as isotretinion,[68]

cranberry products[69]

and employed in the evaluation of residual solvents in betamethasone

valerate.[70]

For analysis of impurities of pharmaceuticals gas chromatography plays an

important role. Recently, to estimate the process related impurities of the pharmaceuticals GC

has been applied,[71-73]

residual solvents listed as impurity by the International Conference of

Harmonization (ICH) are screened by the GC using a variety of detectors.[74-75]

2.3. SPECTROSCOPIC TECHNIQUES

2.3.1. Spectrophotometry

Another valuable group of strategies which find a critical region in pharmacopoeias are

spectrophotometric techniques based totally on natural UV absorption and chemical



782

reactions.[76]

Spectrophotometry is nothing but the quantitative measurement of the reflection

or transmission properties of a material with the help of wavelength.

The advantages of these techniques are low time and laborious. The precision of these

techniques is also excellent. The use of UV–Vis spectrophotometry particularly applied in the

analysis of pharmaceutical dosage form has increased quickly over the last few years.[77-78]

The colorimetric methods are usually depends on the following aspects:

Oxidation-reduction process.

Complex-formation reaction.

A catalytic effect.

It is essential to mention that colorimetric techniques are often used for the assay of bulk

materials. For example, the blue tetrazolium assay is used for the evaluation of corticosteroid

drug formulations.[79]

The colorimetric method is likewise exploited for the dedication of

cardiac glycosides and is provided in European Pharmacopoeia. Several approaches the usage

of spectrophotometry for determination of active pharmaceutical ingredients in bulk drug and

formulations were stated and information of these methods are recorded in Table 4.

Derivative spectroscopy uses first or uppermost derivatives of absorbance with respect to

wavelength for qualitative research and estimation. The concept of derivatizing spectral

records became first offered inside the 1950s, while it was shown to have many advantages.

After all, the approach received little consideration primarily due to the complexity of

generating derivative spectra the with the assist of early UV–Visible spectrophotometers. The

preface of microcomputers inside the late 1970’s made it typically convincing to apply

mathematical strategies to generate derivative spectra quickly, effortlessly and reproducibly.

About the application of UV spectrophotometry, the derivative technique has observed its

applications. Additionally, it can be observed in fluorescence spectrometry,

atomic

absorption, fluorimetry and infrared.[80]

The use of derivative spectrometry is not restricted to

important cases, however may be of advantage every time quantitative study of normal

spectra is uncertain. Disadvantage is additionally associated with derivative methods; the

differential degrades the signal-to-noise ratio, in order that some form of smoothing is

required conjunction with differentiation.



783

Table 4: Quantitative analysis of drugs in pharmaceutical formulations by UV–visible

spectrophotometric procedures.[81-96]

Sr.no. Name of drug Dosage form

1. Amiloride Tablet

2. Aceclofenac and Paracetamol Tablet

3. Dapsone Tablet

4. Aceclofenac and Tizanidine Tablet

5. Atenolol, Ibuprofen and Famotidine Tablet

6. Pantoprazole and Domperidone Tablet

7. Norfloxacin And Ornidazole Tablet

8. Acetaminophen and Ascorbic acid Tablet

9. Famotidine and Domperidone Tablet

10. Acetaminophen and Tramadol Tablet

11. Amoxicillin and Cloxacillin Capsule

12. Amitriptyline and chlordiazepoxide Tablet

13. Telmisartanand Ramipril Tablet

14. Benzoic acid Salicylic acid Tablet

15. Caffeine and Paracetamol Tablet

16. Metronidazole and Amoxicillin Mixture

2.3.2. Near infrared spectroscopy (NIRS)

Near infrared spectroscopy (NIRS) is a rapid and non-destructive method that gives multi

thing analysis of just about any matrix. In current years, NIR spectroscopy has gained a huge

appreciation in the pharmaceutical enterprise for raw material testing, product quality control

and technique monitoring. The increasing pharmaceutical interest in NIR spectroscopy is

probably a direct impact on consequence of its major advantages over different analytical

techniques, namely, an easy sample preparation without any pretreatments, the probability of

keeping apart the sample size position by using use of fiber optic probes, and the expectancy

of chemical and physical sample parameters from one single spectrum. The leading

pharmacopoeias have generally approved NIR techniques. The European Pharmacopoeia in

chapter 2.2.40[97]

and United States pharmacopoeias[98]

forward the suitability of NIR

instrumentation for application in pharmaceutical testing.

NIR spectroscopy in mixture with multivariate data analysis opens many exciting approaches

in pharmaceutical analysis, each qualitatively and quantitatively. A wide variety of

publications describing quantitative NIR measurements of active component in intact pills

have been recorded.[99-101]

In addition to the research articles many evaluation articles have

been published bringing up the utility of the NIRS in pharmaceutical analysis.[102]



784

2.3.3. Nuclear magnetic resonance spectroscopy (NMR)

Since the primary report appeared in 1996 describing the utilization of magnetic resonance

chemical analysis to screen for the drug molecules, the sphere of magnetic resonance

primarily based screening has proceeded promptly.[103]

Recently magnetic resonance finds its

application in measurement in order to work out the impurity of the drug[104]

, characterization

of the composition of the drug products and in quantitation of medication in pharmaceutical

formulations and biological fluids[105]

, several reviews on the appliance of magnetic

resonance in pharmaceuticals are revealed.[106-107]

2.3.4. Fluorimetry and phosphorimetry

The pharmaceutical industries unendingly search for the sensitive analytical techniques

exploitation the small samples. Fluorescence spectroscopy is one amongst the techniques that

serve the purpose of high sensitivity while not the loss of specificity or precision. A gradual

increase within the variety of articles on the application of fluorimetry[108-109]

and

phosphorimetry[110]

in measurement of varied medication in dose forms and biological fluids

has been detected within the recent past.

2.5. Electrochemical methods

The application of electrochemical techniques in the analysis of drugs and pharmaceuticals

has increased greatly over thelast few years. An amberlite XAD-2 and titanium dioxide

nanoparticles modified glassy carbon paste was developed for the determination of

imipramine, trimipramine and desipramine. The electrochemical behavior of these drugs was

investigated using cyclic voltammetry, chronocoulometry, electrochemical impedence

spectroscopy and adsorptive stripping differential pulse voltammetry.[111]

The

electrochemically initiated formation of capsaicin-benzocaine adduct causes a linear decrease

in the voltammetric signal corresponding to capsaicin which correlates to the added

concentration of benzocaine.[112]

The electrochemical behavior of clioquinol, a molecule with

a large spectrum of clinical applications, was studied by cyclic, differential pulse and square-

wave voltammetry over a wide pH range using a glassy carbon electrode.[113]

Here the

application of various electrochemical modes in the analysis of drugs and pharmaceuticals is

presented in Table no.5



785

Table 5: Determination of drug by electrochemical Techniques.[114-120]

Technique Drugs determined Remark

Voltametry b-blocker drugs Nafion-coated glassy carbon electrode

Secnidazole Cathodic adsorptive stripping voltammetry

Polarography Nifedipine

Ciclopirox olamine

Amperometry Diclofenac

Verapamil

Potentiometry N-acetyl-L-cysteine

3. CONCLUSION

The main aim of the pharmaceutical drugs is to serve the human to make them free from

potential illness or prevention of the disease. For the medication to serve its meant purpose

they should be free from impurity or different interference that might dangerous to humans.

This review is aimed toward focusing the role of various analytical instruments within the

assay of pharmaceuticals and giving an intensive literature survey of the instrumentation

concerned in pharmaceutical analysis.

4. ACKNOWLEDGEMENTS

The author thank to teachers for providing the guidance during review work.

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