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It also attenuates the stress response to laryngoscopy and decreases excessive hemodynamic effects during recovery and extubation purchase on line kamagra polo erectile dysfunction without pills. The rate of the maintenance infusion should be titrated to achieve the desired level of sedation 296 C purchase 100mg kamagra polo with amex diabetic with erectile dysfunction icd 9 code. Dexmedetomidine also causes muscle flaccidity and prevents opioid- induced muscle rigidity. This muscle relaxant effect is mediated via a central action, not at the neuromuscular junction. Overall, dexmedetomidine administration during anesthesia maintains hemodynamic stability and allows lower doses of anesthetics and opiates to be used, resulting in more rapid recovery from anesthesia and a reduced need for pain medication after procedures, thereby reducing the length of hospital stay. Pharmacokinetics Distribution half-life (t1/2): rapid (6 min) Elimination half-life (t 1/2β): approximately 2 hours Onset of action: within 5 minutes Protein binding: 94%. The unbound fraction of dexmedetomidine is significantly decreased in subjects with hepatic impairment compared with healthy subjects Metabolism: dexmedetomidine undergoes almost complete hydroxylation through direct glucuronidation and oxidative metabolism via the cyto- chrome P450 system in liver Elimination: the major excreted metabolites are N-glucuronides and N-methyl O-glucuronide dexmedetomidine. These metabolites are inactive and excreted in the urine (approximately 95%) and in the feces (4%) Drug-Drug Interactions ● In vitro studies in human liver microsomes demonstrated no evidence of cytochrome P450-mediated drug interactions that were of clinical relevance ● Coadministration of dexmedetomidine with anesthetics, sedatives, hypnotics, and opioids is likely to lead to an enhancement of their effects. Overall, the most frequently observed adverse events included hypotension (30%), hypertension, nausea/vomiting (11%), sinus bradycardia (8%), atrial fibrillation (7%), fever, hypoxia (6%), sinus tachycardia, and anemia (3%). A bipha- sic cardiovascular response has been described after the administration of dexmedetomidine. Transient hypertension has been observed, primarily during the loading dose in association with the initial peripheral vasoconstrictive effects of dexmedetomidine, and may be associated with the rate of infusion. This initial response lasts for 5 to 10 minutes and is followed by a slight decrease in blood pressure caused by the inhibition of the central sympathetic outflow. The presynaptic α2-adrenoceptors are also stimulated, decreasing nore- pinephrine release, resulting in a fall in blood pressure and heart rate. Because dexme- detomidine decreases sympathetic nervous system activity, hypotension and/or bradycardia may be expected to be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension, or patients with fixed stroke volume. Caution should also be used in patients with preexist- ent severe bradycardia and conduction problems, in patients with reduced ventricular function (ejection fraction > 30%), and in patients who are hypo- volemic or hypotensive. Predictable, dose-dependent decreases in heart rate and blood pressure are observed during infusions. The transient hyperten- sion can generally be attenuated by reducing the infusion rate. If medical intervention is required for hypotension or bradycardia induced by α2 agonism, treatment may include decreasing or stopping the infusion of 298 C. Central Nervous System Dexmedetomidine is an adrenoceptor agonist that has been used for its sedative, anxiolytic, and analgesic properties and does not produce respiratory depres- sion because of its nonopioid mechanism of analgesia. Dexmedetomidine has a 1600-fold greater affinity for the α2-receptor compared with α1-receptors. The sedative effects of α2-adrenoceptor activation have been attributed to the inhibition of this nucleus. Stimulation of the receptors in the brain and spinal cord inhibits neuronal firing, causing hypotension, bradycardia, sedation, and analgesia. Qualitatively, dexmedetomidine induces a sedative response that exhibits properties similar to natural sleep. Patients receiv- ing dexmedetomidine experience a clinically effective sedation, yet are still easily and uniquely arousable and alert when stimulated from sedation and quickly return to their sleep-like state,36 an effect not observed with any other clinically available anesthetic or sedative. Dexmedetomidine lacks amnesic properties, and an overzealous reduction in the anesthetic dose because of suppression of hemodynamic responses to surgical stimulus may lead to awareness. Parenteral,epidural, and intrathecal place- ment cause analgesia and synergistically enhance opioid analgesia, decreasing their side effect of respiratory depression. The reduction of central sympathetic activity by α2 agonists decreases the extent of neuronal damage. Respiratory Dexmedetomidine has no deleterious clinical effects on respiration and produces no clinically apparent respiratory depression36 when used in doses that are sufficient to provide adequate sedation and effective analgesia in the 12. Sedative Hypnotic and Anesthetic Agents 299 surgical population requiring intensive care. There are no clinically important adverse effects on respiratory rate or gas exchange. Dexmedetomidine can be continued safely in the extubated, spontaneously breathing patient. Although dexmedetomidine is dosed to effect, dosage reduction may be necessary in patients with hepatic impairment. Dexmedeto- midine pharmacokinetics are not significantly different in subjects with severe renal impairment (creatinine clearance <30mL/min) compared with healthy subjects. Other Infrequent, but clinically relevant systemic adverse events reported in 1% patients are diaphoresis, hypovolemia, light anesthesia, and rigors. Most of these adverse effects occur during or briefly after bolus dose of the drug. Withdrawal Symptoms After chronic administration, dexmedetomidine could potentially lead to with- drawal symptoms similar to those reported for another α2 adrenergic agonist, clonidine: nervousness, agitation, and headaches, accompanied or followed by a rapid rise in blood pressure and elevated catecholamine concentrations in the plasma. It should be used during pregnancy only if the potential benefits justify the potential risk to the fetus. Standard Concentrations and Compatible Diluents Dexmedetomidine hydrochloride is the S-enantiomer of medetomidine and is chemically described as (+)-4-(S)-[1-(2, 3-dimethylphenyl) ethyl]-1H- imidazole monohydrochloride. Dexmedetomidine is available in 2-mL vials and is a clear, colorless, isotonic solution freely soluble in water with a pH of 4. Dexmedetomidine has been shown to be compatible when administered with lactated Ringers, 5% dextrose in water, 20% mannitol, thiopental sodium, etomidate, depolarizing and nondepolarizing neuromuscular blockers, glycopyrrolate bromide, atropine sulfate, midazolam, morphine, fentanyl, and a plasma substitute. Future of Dexmedetomidine Intrinsic anesthetic properties and effects of dexmedetomidine can be selectively reversed by administering the α2-adrenoceptor antagonist atipamezole (A-17). This drug reverses sedation and sympatholysis caused by dexmedetomidine and has a half-life of 1. The combination of dexmedetomidine and atipamezole might be the basis for a “reversible intrave- nous anesthetic technique. This technique could provide timely and independent recovery from anesthesia and sedation in the future. Mechanism of Action Remifentanil is a synthetic opioid, piperidine derivative, and a hydrochloride salt of 3-(4-methoxycarbonyl-4-[1-oxopropyl phenylamino]-1-piperidine) propanoic acid, methyl ester. Sedative Hypnotic and Anesthetic Agents 301 If postoperative pain is anticipated, adequate analgesia should be initiated before the discontinuation of the remifentanil infusion. The use of remifentanil as the sole induction agent is limited by variable sensitivity and associated side effects. For effective induction of loss of conscious- ness, a hypnotic agent should be combined with 0. In children aged 2 to 7 years old and breathing spontaneously, there is a large variation (0. Reduction in respi- ratory rate (< 10 breaths per minute) seems to be the best predictor of apnea. Pharmacokinetics A pharmacokinetic study in children aged 0 to 18 years old suggested a profile similar to that of adults: Volume of distribution: small (100 mL/kg in adults) Distribution phase: rapid Half-life: mean of 3.
Development of a freeze-dried formu- lation of insulin-loaded chitosan nanoparticles intended for nasal administration cheap kamagra polo 100mg with amex erectile dysfunction pills wiki. Gelatin behaviour in dilute aqueous solution: Designing a nanoparticulate formulation generic kamagra polo 100mg on-line erectile dysfunction treatment medicine. Microencapsulation by solvent extraction/evaporation: Reviewing the state of the art of microsphere preparation process technology. Formulation of l-asparaginase-loaded poly(lactide-co-glycolide) nanoparticles: Inﬂuence of polymer properties on enzyme loading, activity and in vitro release. Development and characterization of protein-loaded poly(lactide-co-glycolide) nanospheres. Ultradeformable lipid vesicles can penetrate the skin and other semi-permeable barriers unfragmented. Biological activity and characteristics of triamcinolone-acetonide for- mulated with the self-regulating drug carriers, Transfersomes (R). Ultraﬂexible vesicles, Transfersomes, have an extremely low pore penetration resistance and transport therapeutic amounts of insulin across the intact mammalian skin. Transdermal immunization with large proteins by means of ultradeformable drug carriers. Transdermal immunisation with an integral membrane component, gap junction protein, by means of ultradeformable drug carriers, Transfer- somes. Formulation of interleukin-2 and interferon-alpha con- taining ultradeformable carriers for potential transdermal application. The effect of cholate on solubilisation and permeability of simple and protein-loaded phosphatidylcholine/sodium cholate mixed aggregates designed to mediate transdermal delivery of macromolecules. Permeabilisation and solubilisation of soybean phosphatidylcholine bilayer vesicles, as membrane models, by polysorbate, Tween 80. Anti-inﬂammatory effects of locally applied enzyme-loaded ultradeformable vesicles on an acute cutaneous model. Ethosomes – Novel vesicular carriers for enhanced delivery: Characterization and skin penetration properties. A clinical evaluation of a novel liposomal carrier for acyclovir in the topical treatment of recurrent herpes labialis. Interactions of elastic and rigid vesicles with human skin in vitro: Electron microscopy and two-photon excitation microscopy. The in vivo and in vitro interactions of elastic and rigid Vesicles with human skin. Liposomal recombinant human superoxide dismutase for the treatment of Peyronie’s disease: A randomized placebo-controlled double-blind prospective clinical study. Genes are introduced into cells or tissues either to inhibit undesirable gene expression or to express therapeutic proteins (3). Target disease states for gene delivery can be broadly categorized into two major classes: inherited and acquired. The two standard procedures used in gene delivery are addition/replacement and ablation (4). While performing the former, a normal gene is introduced into the cell type to replace activity of the defective gene (4). Whether one performs ex vivo or in vivo gene therapy, important focal points are duration of expression of the gene or therapeutic protein and speciﬁcity in deliv- ering the gene to the site of action with minimal adverse effects (1–3). Currently, genes packaged in viral vectors, such as retrovirus, adenovirus, adeno-associated virus, and herpes simplex virus, remain the leading therapeutic candidates for gene therapy, as they have produced functional improvements in several animal models of previously mentioned genetic diseased states. However, because of the risk fac- tors (pathogenicity, immunogenicity) associated with viral vectors, a major empha- sis has been placed on the formulation of nanoparticulate drug delivery vehicles for gene delivery (3). The term “nanometer” in the metric scale of linear measurement refers to one- billionth of a meter. According to National Nanotechnology Initiative, nanotechnol- ogy is deﬁned as research and technology resulting in “the controlled creation and usage” of unique small particles, varying from 1 to 100 nm in length. Looking at the biological systems, it is evident that they are composed of inherent “nanoblocks. This chapter focuses on the formulation of nanoparticulate drug delivery systems for gene delivery. The gene-loaded gold nanoparticles target the cells at a critical velocity that can puncture the cell membrane, and ultimately release the genes into the cell nucleus (9). This method, which involves physical transfer of genes, has the potential to replace the traditional transfection techniques characterized by dismal efﬁciency rates and immunotoxicity (9). It is to be noted, however, that original gene gun suffers from lack of precision and can crush the cells due to “sticking of gold par- ticles (pit damage)”. To overcome these pitfalls, Pui and Chen’s laboratory, at Uni- versity of Minnesota, devised a similar gene gun by using the patented technique called “continuous gene transfection” (9). As reported by Pui and Chen, the gold particle–coated gene composite is loaded into a capillary with the help of a syringe. The applied electric ﬁeld forces the gene suspension or spray out of the capillary at a constant velocity. The suspension is a complex mixture of “highly charged and dispersed gene-coated particles” (9). As mentioned before, the unusually high repelling velocity of similarly charged particles tear the cell membrane and “unload the genes into the cells” (9). Also, there is reduced or no risk of immunotoxicity and the cells can be transfected with plasmids as often as desired. Another added advantage is the possibility of incorporating multiple genes encoded by different plasmids (10). The potential problem of nons- electivity can be addressed by tagging the gold particles with speciﬁc antibodies. However, translat- ing this potential into reality is difﬁcult, as it is extremely tricky to deliver these short nucleotides to the site of action without degradation. Although, in nascent stage, polycation-based gene delivery shows promise in vitro and in vivo studies. However, these systems usually suffer from low sol- ubility and poor bioavailability (8). To circumvent these problems, scientists have developed a new class of nanoparticulate-based drug delivery systems known as nanocochleates (13). Originally developed by Papahadjopoulos in 1974 as an inter- mediate in the preparation of large unilamellar vesicles, the modiﬁed versions of nanocochleates (diameter range, 30–100 nm) are stable drug delivery vehicles for gene and drug delivery whose structure and properties differ enormously from those of liposomes (13). It comprises a puriﬁed calcium (or any other divalent cation, such as zinc, magnesium, or barium)–soy-based phospholipid, with lipids accounting for three- fourths of the weight. Different lipids that make up the nanocochleates include phosphotidyl serine, dioleoylphosphatidylserine, phosphatidic acid, phosphatidy- linositol, phosphatidyl glycerol, phosphatidyl choline, phosphatidylethanolamine, diphosphotidylglycerol, dioleoyl phosphatidic acid, distearoyl phosphatidylser- ine, and dimyristoyl phosphatidylserine, dipalmitoyl phosphatidylgycerol, or a mixture of one or more of these (13).
Their unusual chromosome organization in directional gene clusters previously reported to L order 100 mg kamagra polo otc erectile dysfunction video. Moreover buy cheap kamagra polo 100 mg online erectile dysfunction doctor in hyderabad, the regulation of gene expression is not presumably done at the level of transcription initiation as the rate of polycistronic transcription seems to be stable (Clayton, 2002). Even though the mechanisms of how kinetoplastid parasites regulate gene expression are not fully understood, this appears to involve: the 8 Chapter I Leishmania spp. Moreover, the lower pK values of trypanothione compared to glutathione are coincident with the intracellular pH of the parasites (Moutiez et al. The trypanothione reductase play an important role in the parasites redox state as it is the responsible of maintaining the trypanothione pool reduced. The transmission of leishmaniasis is attributed to about 70 of around 1000 known sandfly species (Murray et al. Those belonging to the genus Lutzomya are prevalent in the New World (ie, the Americas), and those belonging to the genus Phlebotomus are prevalent in the Old World (ie, Africa, Europe and Asia). Phlebotomine sandflies are not active during the day and seek out cool and relatively humid dark niches which allow them to survive in hot and dry climates. Leishmania infections typically occur through the bite of sandflies belonging to either Phlebotomus spp. The classification of the mammal-infective Leishmania into subgenera, Leishmania and Viannia, was originally based on the vector gut parts colonized by the parasites (Lainson et al. Leishmania (Leishmania) parasites are transmitted to either female Phlebotomus (Old World) or Lutzomya (New World) species while Leishmania (Viannia) species are only found in the New World and therefore all the vectors are Lutzomya species (Bates, 2007). The ingestion of a blood meal containing Leishmania amastigotes by the female sandfly induces the amastigotes’ transformation into procyclic promastigotes, a weakly motile and replicative form that multiplies in the blood meal confined by the periotrophic matrix, a mesh of proteins and chitin secreted by the insect midgut. Few days later, the parasites slow their replication and differentiate into strongly motile promastigotes that break the blood meal’s periotrophic matrix and migrate. The species belonging to the subgenus Leishmania move towards the anterior midgut and some attach to the microvilli of the midgut’s epithelium, while the species belonging to the Viania subgenus can be found in the pyloric region of the hindgut (Walters et al. Differences in the ability to inhibit or to resist killing by proteolitic enzymes released into the vector midgut after blood feeding, and/or to remain in the gut during excretion of the digested blood meal define vector competence in most species. The natural transmission of leishmaniasis is mediated by the bite of an infected female sandfly when she has a blood feeding. The sandfly saliva is required for the blood feeding due to its potent vasodilator and anti-haemostatic properties (Ribeiro, 1987). Furthermore, it is a disease exacerbation factor, at least for cutaneous leishmaniasis (Titus and Ribeiro, 1988). Co-inoculation of sandfly saliva and parasites led to disease exacerbation in several studies, which seems to be related with the modulation of the immune system to favor parasite survival and replication (Kamhawi, 2000; Rohousova and Volf, 2006). By contrast, the bites of uninfected sand flies or the vaccination with salivary gland extracts induce T cell mediated protection against an experimental challenge and disclose its potential for vaccination (Belkaid et al. Furthermore, in infected humans, anti-saliva antibodies are detected (Gomes et al. Visceral leishmaniasis can be induced through blood containing amastigotes (shared needles, transfusion, transplacental spread) or organ transplantation (Morillas- Marquez et al. The several Leishmania species that cause disease in humans have a zoonotic transmission, with the exception of L. However, even for these species, some animal reservoirs in endemic areas have recently been identified (Dereure et al. Furthermore, the different Leishmania species do not seem to exhibit reservoir strain or specie specificity, unlike what happens with the sandfly. Indeed, certain Leishmania species are maintained by several hosts, and several Leishmania species may be found in the same host (Saliba et al. This disease is prevalent in the Central and South America, Mediterranean basin and Asia. Dogs are the main domestic reservoirs while jackals, foxes and wolves are the sylvatic ones (for review see Gramiccia and Gradoni, 2005). However, unusual Leishmania animal hosts such as cats and equines have recently been identified in those endemic areas (for review see Mancianti, 2004). The role of cats is still under debate, but they seem to be secondary reservoirs, while equines are incidental hosts (Gramiccia and Gradoni, 2005). The large spectrum of clinical manifestations reflects leishmaniasis’ complexity, mainly associated with the number of Leishmania species that cause disease, as well as many sandfly and mammalian species indicated as vectors and reservoirs, respectively. This could indeed be due, in part, to improved diagnostic and case notification, but inadequate vector and reservoir control, increased detection of cutaneous leishmaniasis associated with opportunistic infections (e. Cutaneous leishmaniasis in endemic areas affects mainly children of up to 15 years of age, and the main risk factors besides age are household design and construction materials, and the presence of domestic animals (Reithinger et al. Indeed, several authors refer to them as synonyms, despite the disagreement of others (Shaw, 1994; Lukes et al. Furthermore, they present high parasite loads in organs, low sensitivity to the serological-based diagnostic tests and treatment failure (Murray et al. Therefore, specific and sensitive tests are very important, not only for a prompt and accurate diagnosis but also for a successful treatment and subsequent disease control. Occasionally, the culture of biopsy triturates or aspirates is 15 Chapter I Leishmania spp. Even though it is very specific, the sensitivity of this method is highly variable and depends largely on the number and dispersion of parasites in the biopsy, the technical skills of the personnel, the sampling procedure and the sample origin (Herwalt, 1999). However, spleen aspirates require considerable technical expertise, since life threatening haemorrhages can occur (Kager et al. Furthermore, the possibility of identifying the Leishmania specie and predicting the disease severity and treatment outcome is becoming important in the patients’ clinical management (Murray et al. One is related to the persistence of the anti-Leishmania antibodies for long periods of time after the cure (Hailu, 1990;De Almeida Silva et al. These tests should therefore be used in combination with clinical symptoms for an 16 Chapter I Leishmania spp. The several limitations of the poor Leishmania endemic areas have boosted the development of diagnostic tests that could be used in the field: easy to perform, cheap, reproducible and rapid. Although, improvements concerning the test sensitivity are required (Chappuis et al. A brief overview of each approach will be given, but treatment options, due to their relevance in the scope of this thesis, will be dealt with in more detail in the next chapter. However, there are some endemic regions, such as Sudan and East Africa, where this type of control measures is not effective, since the vector feeding occurs mainly outside (Hassan et al. Furthermore, economic constrains limit the efficiency and applicability of these control measurements. In the regions where dogs are domestic reservoirs of Leishmania, the use of deltamethrin impregnated collars revealed to be effective in reducing the risk of infection in dogs and children (Reithinger et al. This strategy seems feasible and effective, since the killing of sero-positive animals is not well accepted by ethical reasons and its efficiency is even debated (Ashford et al. Furthermore, the treatment of infected dogs is not an efficient measure not only due to frequent relapses but also to the development of drug resistances (Alvar et al.
To Distinguish and Characterize the pri- order kamagra polo australia erectile dysfunction at the age of 28, sec- and tert-amine Salts from One Another order cheap kamagra polo on-line erectile dysfunction drugs reviews............................................................................................ Determination of Specific Organic Compounds as Impurities in Official Pharmaceutical Substances............................................................... Medicinal chemists, pharmacologists, biochemists, analytical chemists and medical professionals have paved the way with their single goal objective to combat the sufferings of human beings. In this integrated effort the role of an analyst vis-a-vis the chemical purity of pharmaceutical substances and drugs made therefrom and finally the dosage forms that are usually available for direct patient’s usage, has become not only extremely crucial but also equally important and vital. As on date product safety has to be an integral part of all product research in pharmaceutical substances. Inspite of all the qualified successes of synthetic drug research achieved in the last four decades to combat infectious diseases of the more than 80,000 different ailments, unfortunately only about one third can be treated with drugs, most of them only symptomatically. In order to meet these challenges one needs to adopt novel approaches in pharmaceutical research. Both molecular biology and genetic engineering will be exploited duly in opening up new routes. It is, however, pertinent to mention here that pharmaceutical chemicals must maintain a very high degree of chemical purity. It is quite obvious that a state of absolute purity may not be achievable, but a sincere effort must be exercised to obtain the maximum freedom from foreign substances. Bearing in mind the exorbitant operational costs to attain the ‘highest standards’ of purity, perhaps some of these processes are not economically viable. Therefore, a compromise has got to be made to strike a balance between the purity of a substance at a reasonably viable cost and at the same time its purity e. In short, a host of impurities in pharmaceutical chemicals do occur that may be partially responsible for toxicity, chemical interference and general instability. In this chapter, the purity and management of pharmaceutical chemicals, would be discussed briefly so as to take adequate cognizance of the importance of standardization of these substances, in addition to their management by Official Methods. The standards for pharmaceutical chemicals and their respective dosage forms, as laid down in, various Official Compendia fulfil broadly the following three cardinal objectives, namely : (a) Broad-based highest attainable standard, (b) Biological response versus chemical purity, and (c) Offical standards versus manufacturing standards. A wide variation of active ingredients ranging between 90% in one sample and 110% (± 10 per cent limit) in another sample could invariably be observed. Therefore, it has become absolutely essential to lay down definite standards so as to ensure that : • Different laboratories may produce reasonably reproducible products. Examples : (i) Substances to be stored in well-closed, light-resistant containers e. It is a well-known fact that a pharmaceutical substance can be prepared by adopting different routes of synthesis based upon the dynamic ongoing research in the field of organic-reaction-mechanisms. Relentless efforts are exerted vigorously by reputed research laboratories across the world to look for shorter routes of synthesis bearing in mind the cost-effectiveness of the final product. Nevertheless, the latter product is more in demand because it is completely devoid of bromine residues in the final product. During the process of manufacture an unavoidable criterion is the loss of active ingredients. Therefore, all Official Standards for pharmaceutical chemicals and dosage forms should accomodate such losses caused due to loss in manufacture, unavoidable decomposition and storage under normal conditions for a stipulated period. Official standards with regard to dosage form and packs, preservation and prevention from contamination in a variety of pharmaceutical products, such as eye-drops, multidose injections and antiseptic creams (external application) that may be prone to spoilage with prolonged repetitive usage should be well defined. Hence, all pharmaceutical chemicals and finished products must rigidly conform to the laid-out standards in a particular country and are subjected to various checks at different levels either by Government/State owned drug testing laboratories or by Government/State approved drug testing laboratories. Official Compendia for pharmaceutical substances usually include the following parameters, namely : • Description of the Drug or Finished Product • Identification Tests • Physical Constants • Assay of Pharmaceutical Substances • Assay of Principal Active Ingredients in Formulated Dosage Forms • Limit Test • Storage Conditions 1. In other words, the accuracy and significance of measurements may be solely limited by the sampling process. Unless and until the sampling process is performed properly, it may give rise to a possible weak link in the interpretation of the analytical results. However, a good deal of the wisdom of the analyst supported by the application of statisical results and wealth of experience may go a long way in achieving reasonably accurate and reproducible results. Sampling Procedures Samples may be categorized broadly into four heads, namely : (a) Gross Sample : A sample that represents the whole lot and may vary from a few grams or less to several pounds based on the nature of the bulk material. For Solids Sampling of solid materials are comparatively more difficult than other materials because of the follow- ing three reasons, namely : (a) Variation in particle size. Sampling of solids can be best accomplished by adopting the following procedures : • To take 1/50 to 1/100th of the total bulk for gross samples. For Liquids Sampling of liquids may be carried out by following these procedures : • Small heterogenous liquid samples are first shaken thoroughly and then followed by immediate sampling. However, the latter method is preferred for obvious reasons since the analysis shall have a better hold on the accuracy and precision of the analysis. A few specific examples are stated below : (a) A 24 hour urine sample collections are usually more reliable than single specimens. For example : (a) A breathe sample may be collected by allowing the subject to blow into an evacuated bag. Errors The famous adage—‘to err is human to forgive divine’—literally means that it is natural for people to make mistakes. However, errors in analytical chemistry or more precisely in pharmaceutical drug analysis are normally of three types, namely : (a) Determinate Errors (b) Instrumental Errors (c) Personal Errors These above mentioned errors would be discussed briefly here with specific examples. It is pertinent to mention here that errors outside the range of ‘permissible errors’ in the analyses of pharmaceutical substances may cause serious problems because most of these substances are usually highly toxic, potent and used exten- sively in life-saving processes across the globe. Determinate Errors Errors caused due to either incorrect adoption of an assay method or an incorrect graduation read out by an analyst are termed as determinate errors. In usual practice the determinate errors are subtle in nature and hence, not easily detected. A few typical examples of determinate errors are stated below : (a) Gravimetric Analysis : Where a compound is precipitated from a solution and the analyst believes that the analyte has been removed from the solution completely. Actually a small portion of the substance under investigation shall remain in solution. It may require an excess quantity of reagent to affect the colour change which ultimately shows completion of the chemical reaction between reagent and analyte. Therefore, in all such analytical procedures a ‘blank titration’ is performed simultaneously to determine how much reagent is required to affect the colour change when no analyte is present. Instrumnetal Errors The past three decades have witnessed a quantum progress and advancement in the field of analytical chemistry. Nowadays, both microprocessor based and computer-aided analytical instruments have more or less replaced the manually operated ones in any reasonably good analytical laboratory. One of the most prevalent determinate errors is caused by analytical intruments which are found to be ‘out of calibration’. Hence, it is very essential that such instruments need to be calibrated periodically, for instance, a pH meter is calibrated using a buffer solution of known pH, say adjusting the meter to read pH = 7. Personal Errors In addition to errors caused due to improper assay methods or faulty instruments, it may also be due to the analyst. A few typical examples are cited below : (a) Physical Impairment : A person suffering from colour blindness may not be in a position to assess colour-changes precisely ; or if he uses bifocals he may not take the burette readings accurately.